As a leading cause of morbidity and mortality globally, sepsis continues to pose a significant clinical challenge. Gram-negative bacteria make up a large percentage of sepsis-related infections among the various microbial offenders, especially in hospitalized and critically ill populations. These pathogens, which include Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and others, have developed a variety of virulence mechanisms and antibiotic resistance patterns that not only make diagnosis and treatment more difficult but also have a substantial impact on patient outcomes. Gram-negative sepsis has drawn more attention in the fields of clinical medicine and infectious disease research due to its rising incidence in both community-acquired and healthcare-associated infections ^[1].

The distinctive cell wall structure of gram-negative bacteria is defined by an outer membrane that contains lipopolysaccharides (LPS), also known as endotoxins. This endotoxin is essential to the pathophysiology of sepsis because it sets off a series of inflammatory reactions in the host's immune system. When toll-like receptor 4 (TLR4) recognizes LPS, pro-inflammatory cytokines such interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are released, causing systemic inflammation. Although the goal of this response is to confine the infection, it frequently gets dysregulated, leading to tissue hypoperfusion, endothelial dysfunction, microvascular thrombosis, and finally multi-organ dysfunction syndrome (MODS). As a result, the clinical range of gram-negative sepsis includes fulminant septic shock, which has a significant risk of death, as well as moderate systemic symptoms^[2,3]

Early detection of gram-negative sepsis is crucial since its clinical manifestation is frequently non-specific and can resemble other systemic diseases. Common symptoms include fever, chills, hypotension, tachycardia, tachypnea, altered mental status, and indications of compromised organs. Urinary tract infections, intra-abdominal infections, pneumonia, bloodstream infections associated with catheter use, and wound infections are among the most common foci. In nosocomial settings, where extended hospital stays, invasive procedures, and the use of broad-spectrum antibiotics encourage colonization and infection by multidrug-resistant (MDR) strains, gram-negative organisms are especially notorious^[4] The clinical profile of patients with gram-negative sepsis frequently includes multiple predisposing factors. In nosocomial settings, where extended hospital stays, invasive procedures, and the administration of broad-spectrum antibiotics encourage colonization and infection by multidrug-resistant (MDR) strains, gram-negative microbes are especially infamous ^[4]. Patients with gram-negative sepsis frequently have a number of risk factors in their clinical profile.

Common causes include advanced age, underlying chronic conditions such diabetes mellitus, cancer, chronic kidney disease, and immunosuppression brought on by corticosteroids or chemotherapy. Gram-negative infection risk is increased by central venous catheterization, mechanical ventilation, intensive care unit (ICU) admission, and previous antibiotic exposure. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Klebsiella pneumoniae, and metallo-beta-lactamase-producing Pseudomonas are among the MDR organisms that are becoming more common. Delaying appropriate antimicrobial therapy is known to be a predictor of unfavorable outcomes ^[5].

Gram-negative sepsis is diagnosed based on clinical suspicion that is confirmed by microbiological and laboratory tests. Although findings frequently take 48 to 72 hours, blood cultures are still the gold standard for determining the causal organism. Early pathogen detection has been improved by rapid diagnostic tests including matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and polymerase chain reaction (PCR)-based techniques. Despite their lack of specificity, biomarkers like procalcitonin and C-reactive protein (CRP) are widely employed to support clinical assessment and track treatment response.

The timing and appropriateness of antibiotic therapy, host immunological condition, the presence of comorbidities, the site and severity of infection, and the requirement for organ support are some of the linked aspects that affect the outcomes of patients with gram-negative sepsis. Improving prognosis requires early goal-directed therapy, which includes intensive fluid resuscitation, vasopressor support, timely delivery of empiric broad-spectrum antibiotics, and source control (e.g., drainage of abscesses, removal of infected devices). Nevertheless, fatality rates in severe gram-negative sepsis and septic shock are still startlingly high, ranging from 20% to 60% depending on the situation, even with the best care ^{[6, 7]}.

There is growing evidence that gram-negative sepsis's immunological and inflammatory dysregulation may have long-term effects on survivors. These highlight the necessity of post-acute care and follow-up and include neurocognitive impairment, persistent organ malfunction, and increased vulnerability to recurrent infections. Additionally, patients and their families bear an additional burden due to the psychological effects of sepsis, such as depression, post-traumatic stress disorder (PTSD), and a lower quality of life.

Study Design This study was conducted as a prospective observational study. It was designed to systematically document and evaluate the clinical characteristics and outcomes of patients diagnosed with Gram-negative sepsis. The observational nature allowed for data collection in real time without any interventional manipulation, ensuring the authenticity of clinical presentations, diagnostic measures, and treatment outcomes. Patients were followed up throughout their hospital stay to determine disease progression, organ dysfunction, and survival. Study Setting The study was carried out at the Department of General Medicine, Shimoga Institute of Medical Sciences (SIMS), situated within McGann Hospital, Shivamogga. This institution functions as a tertiary care center that serves both rural and urban populations in Karnataka. The hospital's infrastructure included emergency, intensive care, and diagnostic support that facilitated comprehensive sepsis care and enabled the implementation of this study within a real-world clinical setting. Study Duration The study spanned a total duration of 18 months, starting in March 2024 and concluding in August 2025. This time frame was sufficient to capture seasonal variations in infection rates and allowed for the inclusion of a representative sample of patients presenting with Gram-negative sepsis over more than one calendar year. Inclusion Criteria • Patients aged above 18 years and below 80 years. • Patients with suspected or documented sepsis fulfilling the Sequential Organ Failure Assessment (SOFA) score ≥2 criteria. Exclusion Criteria • Patients diagnosed with infections of viral, fungal, parasitic, or protozoal origin. • Patients not meeting the diagnostic criteria for sepsis. • Mentally unsound patients or those unwilling to provide informed consent. • Patients requiring immediate surgical intervention. These criteria ensured that the study specifically focused on adult patients with Gram-negative bacterial sepsis while excluding confounding pathologies and ethical complexities. Study Sampling Convenience sampling was employed for this study. All eligible patients presenting with Gram-negative sepsis during the study period were screened and recruited consecutively based on the inclusion and exclusion criteria. This non-randomized sampling method enabled the capture of a real-time clinical cohort and facilitated continuous enrollment as patients presented to the hospital. Methodology Patients presenting to McGann Hospital with suspected or confirmed Gram-negative sepsis were evaluated for eligibility based on the inclusion and exclusion criteria. Written informed consent was obtained from all participants or their legally authorized representatives. A structured clinical assessment was then conducted, which included a detailed history (symptom duration, comorbidities, and prior treatments), physical examination, and systemic evaluation. Following this, relevant laboratory and imaging investigations were carried out. The SOFA score was calculated upon admission and monitored throughout the hospital stay. The study was approved by the Institutional Ethical Committee of Shimoga Institute of Medical Sciences. Ethical clearance was obtained prior to the commencement of patient recruitment. All participants provided written informed consent after being thoroughly informed about the study's purpose, potential risks, and benefits in their native language.

The study included 91 patients with gram-negative sepsis. The highest proportion of patients belonged to the >60 years age group with 28 cases (30.8%), followed by 46–60 years with 27 patients (29.7%). The <30 years and 31–45 years age groups each comprised 18 patients (19.8%), indicating a higher representation of older individuals in the study population.

Table 1: Age-wise Distribution of Study Participants

Graph 1: Age-wise Distribution of Study Participants

Gender Distribution of Study Subjects

Among the 91 study participants, males constituted a slightly higher proportion with 50 cases (54.9%), while females accounted for 41 cases (45.1%). The distribution indicates a modest male predominance in the study population, with both genders being substantially represented among patients diagnosed with gram-negative sepsis.

               Table 2: Gender Distribution of Study Subjects

Distribution of Co-morbidities among Study Participants

Analysis of co-morbidities showed diabetes mellitus as the most frequent condition, present in 28 patients (30.8%), followed by hypertension in 24 patients (26.4%). COPD was observed in 15 patients (16.5%). Other co-morbidities included ischemic heart disease in 7 patients (7.7%), cerebrovascular accident in 6 patients (6.6%), and chronic liver disease and hypothyroidism each in 2 patients (2.2%).

Table 3: Distribution Of Co-Morbidities Among Study Participants

Among the study participants, smoking and alcohol consumption were each reported in 31 patients (34.1%). Tobacco chewing was observed in 9 patients (9.9%). These findings indicate that smoking and alcohol use were the most commonly reported personal habits among the study population, while tobacco chewing was present in a smaller proportion of cases.

Table 4: Distribution of Personal Habits and Social History

Frequency Distribution of Chief Complaints and Symptoms

Fever was the most common presenting symptom, reported in 87 patients (95.6%). Vomiting was observed in 48 patients (52.7%), followed by breathlessness in 34 (37.4%), abdominal pain in 32 (35.2%), and cough in 31 (34.1%). Other symptoms included diarrhoea (31.9%), myalgia (30.8%), arthralgia (28.6%), urinary disturbances (27.5%), sore throat (24.2%), headache and jaundice (22.0%), altered sensorium (20.9%), convulsions (11.0%), rhinitis (7.7%), and photophobia (3.3%), while retro-orbital pain and maculopapular rash were not observed.

Table 6: Descriptive Statistics of Vital Parameters at Admission

 Distribution of General Physical Examination Findings

Among the general physical examination findings, pallor was the most common sign observed in 36 patients (39.6%), followed by edema in 28 patients (30.8%) and icterus in 25 patients (27.5%). Clubbing was present in 19 patients (20.9%). Signs of meningeal irritation were noted in 9 patients (9.9%), lymphadenopathy in 4 patients (4.4%), and cyanosis in 3 patients (3.3%).

The current study's objective was to assess the clinical profile, microbiological spectrum, severity pattern, and outcomes of patients with gram-negative sepsis who were admitted to McGann Hospital, SIMS, Shivamogga. The study was designed to evaluate the following: organ dysfunction, treatment profile, co-morbid conditions, presenting symptoms, admission vital parameters, physical findings, bacterial isolates, laboratory and inflammatory markers, and final clinical outcomes in patients with culture-confirmed gram-negative sepsis. In order to uncover clinically meaningful prognostic indicators in ordinary hospital practice, the study also sought to identify factors related with severity and mortality, such as the role of diabetes mellitus, hypotension, serum lactate, CRP, WBC count, and SOFA score. The significance of this study lies in the fact that gram-negative sepsis remains a major cause of morbidity and mortality in hospitalized patients, particularly in tertiary care settings where older adults, patients with multiple co-morbidities, and those with severe infections are commonly treated. Gram-negative organisms such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli are increasingly recognized as major pathogens because of their virulence, capacity to create severe systemic inflammatory response, and potential for drug resistance Despite this, there is frequently a lack of local information regarding their clinical presentation, laboratory profile, infection source, and results. Because it offers institution-specific data on the prevalence and behavior of gram-negative sepsis in a real-world tertiary hospital population, the current study is significant. The study provides useful recommendations for early diagnosis, risk stratification, monitoring, and care by identifying the main sources of infection, the principal organisms involved, and the factors associated with severity, extended hospital stay, and mortality. It is anticipated that the results will help physicians make better decisions at the bedside, optimize empirical antibiotic therapy, and reinforce sepsis care pathways. This will improve patient outcomes and make hospital-based management of gram-negative sepsis more logical. The present study demonstrated that gram-negative sepsis was more common in older adults. Among the 91 patients included, the highest proportion belonged to the >60 years age group with 28 patients (30.8%), followed closely by the 46–60 years group with 27 patients (29.7%), while the younger age groups <30 years and 31–45 years each comprised 18 patients (19.8%). This shows that nearly two-thirds of the patients were above 45 years of age, indicating that increasing age was an important demographic characteristic in the present cohort. The predominance of older patients may be explained by age-related decline in immune function, a greater burden of chronic comorbid illnesses, repeated exposure to healthcare environments, and reduced physiological reserve to withstand systemic infection. In the present study, males constituted 50 cases (54.9%) and females 41 cases (45.1%), indicating a mild male predominance among patients with gram-negative sepsis. Although both sexes were substantially represented, the slightly higher proportion of males suggests that gram-negative sepsis may affect men somewhat more frequently in this setting. This difference, though not very wide, may be related to greater exposure among men to smoking, alcohol consumption, occupational stress, delayed presentation to hospital, and a higher prevalence of certain chronic illnesses that predispose to infection. The present findings are in agreement with earlier adult sepsis observations. Despite its important findings, the present study has certain limitations that should be acknowledged while interpreting the results. First, the study appears to have been conducted at a single tertiary care center, which may limit the generalizability of the findings to other hospitals, regions, or healthcare settings with different patient populations, referral patterns, and microbial ecology. Second, the sample size of 91 patients, although adequate for descriptive analysis, is relatively modest for more detailed subgroup comparisons, particularly pathogen-wise mortality analysis and source-specific outcome assessment. Small numbers in some organism categories may have reduced the statistical power to detect significant differences. Third, the study primarily reflects hospitalized adult patients and therefore may not be directly applicable to pediatric, neonatal, or community-based sepsis populations. Interventional studies evaluating antimicrobial stewardship programs, protocol-based sepsis pathways, and early warning systems would also be highly relevant. Overall, future research should aim not only to describe gram-negative sepsis but to build practical strategies for earlier detection, better prognostic stratification, rational antibiotic use, and improved patient survival in tertiary care hospitals.

Gram-negative sepsis is a serious multisystem illness that is linked to significant morbidity, organ dysfunction, and in-hospital mortality, according to the current study on clinical profile and outcomes in patients with the disease at Mc Gann Hospital, SIMS, Shivamogga. A total of 91 culture-confirmed cases were analyzed, and the results showed that the disease primarily affected older adults, with the highest proportion seen in the >60 years age group (30.8% males and 45.1% females, indicating that gram-negative sepsis affected both sexes but was somewhat more common in men. According to the co-morbidity pattern, patients with gram-negative sepsis often had serious underlying conditions, especially diabetes mellitus (30.8%) and hypertension (26.4%), with diabetes having a statistically significant correlation with the severity of sepsis (p = 0.0483). These results imply that patients with diabetes and the elderly constitute a particularly susceptible population that needs closer clinical monitoring. Gram-negative sepsis frequently manifests as a febrile multisystem disorder involving respiratory, gastrointestinal, and urinary complaints, as evidenced by the fact that fever dominated the clinical presentation in 95.6% of patients. Other common symptoms included vomiting (52.7%), breathlessness (37.4%), abdominal pain (35.2%), cough (34.1%), and diarrhea (31.9%). With a mean pulse rate of 110.03 bpm, a systolic blood pressure of 99.81 mmHg, a temperature of 38.66°C, and a SpO₂ of 92.87%, the admission vital signs indicated a substantial systemic disease, indicating that many patients were already hemodynamically unstable or physiologically compromised at presentation. Examining patients frequently revealed pallor, edema, and icterus, which further supported the burden of organ involvement and chronic illness.