European Journal of Cardiovascular Medicine

Bloodstream infections (BSIs) are among the most severe clinical conditions encountered in hospital settings, often resulting in prolonged hospitalization, increased healthcare costs, and significant morbidity and mortality. The global burden of BSIs has escalated with the emergence of multidrug-resistant (MDR) organisms, posing challenges for timely diagnosis and effective antimicrobial management^[1]. Infections originating from various sources such as the lungs, urinary tract, gastrointestinal tract, or indwelling catheters can lead to bacteremia or septicemia, which if left untreated or improperly managed, can progress to septic shock and organ failure. This underscores the critical need for early diagnostic indicators that can aid in initiating prompt and targeted therapy before microbiological confirmation is available^[2].

C-reactive protein (CRP) is a hepatic acute-phase reactant synthesized in response to cytokines, particularly interleukin-6 (IL-6), during systemic inflammatory responses. As a nonspecific marker, CRP has long been used to assess the severity and progression of infections, inflammation, and tissue injury. Elevated CRP levels are especially prominent in bacterial infections compared to viral or non-infectious inflammatory conditions. In the context of BSIs, CRP may offer valuable insight into the systemic inflammatory burden and the potential severity of infection^[3]. However, its utility as a correlate for specific bacterial isolates and their resistance profiles remains a subject of ongoing investigation.

India, like many low- and middle-income countries, faces a dual burden of increasing antibiotic resistance and limited access to rapid molecular diagnostics. In such resource-constrained environments, reliance on traditional biomarkers like CRP becomes even more significant^[4]. Identifying a reliable association between CRP levels and bacterial isolate characteristics could assist clinicians in anticipating the nature of the pathogen Gram-positive vs. Gram-negative as well as its potential resistance mechanisms such as extended-spectrum beta-lactamase (ESBL) production or methicillin resistance (MRSA). This could, in turn, improve empirical antibiotic choices before blood culture results become available^[5].

The growing threat of antimicrobial resistance, including ESBL-producing Enterobacteriaceae, carbapenem-resistant organisms, and MRSA, further amplifies the urgency of utilizing accessible diagnostic tools to support early clinical decisions^[6]. While several studies have examined CRP levels in sepsis and systemic infections, few have attempted to directly correlate quantitative CRP values with microbiological outcomes in BSIs, particularly in the Indian population. Furthermore, existing literature lacks consensus on whether CRP levels significantly differ among different classes of pathogens and resistant phenotypes^[7].

This study was thus designed to evaluate the relationship between CRP levels and the type of bacterial pathogen isolated in patients with bloodstream infections. In addition, the study investigates whether CRP can serve as an indirect marker of antimicrobial resistance, thereby aiding in early prediction of infection severity and potential treatment failure. The findings are expected to bridge a critical gap in the literature by correlating inflammatory biomarkers with microbiological profiles in BSIs, potentially contributing to better stratification of septic patients and optimized use of antibiotics in hospital settings

Aim and Objectives

Aim

To evaluate the correlation between serum C-reactive protein (CRP) levels, the type of bacterial isolates, and associated antibiotic resistance patterns in patients with bloodstream infections.

Objectives

1. To measure serum CRP levels in patients with microbiologically confirmed bloodstream infections.
2. To identify and characterize bacterial isolates obtained from blood cultures of these patients.
3. To determine the antibiotic susceptibility profile of the isolated organisms with emphasis on multidrug resistance, ESBL, and MRSA.
4. To correlate CRP levels with the type of bacterial pathogen (Gram-positive vs. Gram-negative).
5. To assess the association between elevated CRP levels and the presence of antimicrobial resistance.
6. To evaluate the potential role of CRP as a predictive marker for pathogen virulence and resistance in bloodstream infections.

Study design

This was a hospital-based, cross-sectional observational study conducted to investigate the correlation between serum C-reactive protein levels and the microbiological characteristics of bacterial bloodstream infections.

Study setting and duration

The study was carried out in the Department of Microbiology and Biochemistry at a tertiary care hospital in India over a period of 18 months, from January 2022 to June 2023.

Sample size

A total of 130 patients with clinically suspected bloodstream infections and confirmed positive blood cultures were enrolled in the study.

Inclusion criteria

• Patients aged ≥18 years with signs and symptoms of systemic infection.
• Blood culture positivity for bacterial pathogens.
• Availability of serum sample for CRP estimation at the time of diagnosis.

Exclusion criteria

• Patients with viral, fungal, or parasitic bloodstream infections.
• Patients with autoimmune diseases, malignancies, or other chronic inflammatory conditions.
• Those receiving immunosuppressive therapy or corticosteroids.
• Incomplete clinical or laboratory data.

Sample collection and processing

Venous blood samples were collected aseptically under sterile conditions before administration of antibiotics. A portion of the sample was sent for CRP estimation and another for blood culture. CRP levels were measured using an immunoturbidimetric assay on a fully automated analyzer following the manufacturer's protocol. The results were recorded in mg/L.

Microbiological analysis

Blood cultures were processed using automated systems (e.g., BacT/ALERT or BACTEC) and subcultured on appropriate media. Bacterial isolates were identified based on colony morphology, Gram staining, conventional biochemical reactions, and confirmed by automated identification systems. Antibiotic susceptibility testing was performed using the Kirby–Bauer disc diffusion method and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The presence of multidrug resistance (MDR), extended-spectrum beta-lactamase (ESBL) production, and methicillin resistance (MRSA) was confirmed using standard phenotypic methods.

Data management and statistical analysis

Patient demographic details, clinical data, CRP values, culture results, and antibiotic sensitivity patterns were recorded in predesigned case record forms. Quantitative variables were expressed as mean ± standard deviation. Comparisons between CRP levels in Gram-positive and Gram-negative infections were analyzed using unpaired t-tests. Correlation between CRP values and antimicrobial resistance patterns was evaluated using Pearson’s correlation coefficient. A p-value of <0.05 was considered statistically significant. All analyses were performed using licensed statistical software.

Ethical considerations

The study protocol was approved by the Institutional Ethics Committee. Informed consent was obtained from all participants or their legal guardians prior to inclusion in the study. Patient confidentiality and anonymity were strictly maintained throughout the research process.

Overview

A total of 130 patients with microbiologically confirmed bloodstream infections were included in the study. Among these, 78 (60%) were male and 52 (40%) females, with a mean age of 51.4 ± 16.2 years. Gram-negative organisms were more frequently isolated compared to Gram-positive organisms. C-reactive protein (CRP) levels were elevated in all patients, with significantly higher levels in those infected with Gram-negative organisms and multidrug-resistant pathogens. The CRP levels demonstrated statistically significant correlations with the type of organism and antibiotic resistance profiles.

Table 1: Demographic Profile of Patients with Bloodstream Infections

Table 1 presents the age and sex distribution of patients enrolled in the study.

Patients across a wide age range were included, with a slight male predominance.

Table 2: Clinical Presentations in Patients with Bloodstream Infections

Table 2 summarizes the major presenting symptoms and signs in the study population.

Fever was the most common presenting complaint, seen in nearly all patients.

Table 3: Distribution of Bacterial Isolates

Table 3 shows the types and frequencies of bacterial isolates recovered from positive blood cultures.

Gram-negative organisms accounted for 70% of all isolates.

Table 4: Gram Stain Classification of Isolates

Table 4 classifies isolates into Gram-positive and Gram-negative organisms.

Gram-negative infections were significantly more prevalent in this cohort.

Table 5: Mean CRP Levels Based on Gram Type

Table 5 compares serum CRP levels between Gram-positive and Gram-negative infections.

CRP levels were significantly higher in Gram-negative BSIs.

Table 6: Antibiotic Resistance Profiles of Isolates

Table 6 shows the resistance characteristics among isolates.

MDR and ESBL-producing organisms formed a considerable subset of isolates.

Table 7: Mean CRP Levels in Relation to Resistance Patterns

Table 7 provides mean CRP levels across different resistance categories.

Elevated CRP levels correlated strongly with drug-resistant strains.

Table 8: Correlation Between CRP and Duration of Fever

Table 8 explores the relationship between CRP levels and duration of febrile illness.

Longer duration of fever was associated with higher CRP levels.

Table 9: Site of Infection and CRP Levels

Table 9 correlates primary infection source with CRP values.

Catheter-related infections had relatively lower CRP values.

Table 10: Correlation Between CRP and Blood Culture Yield Time

Table 10 evaluates whether CRP levels relate to faster culture positivity.

Higher CRP values were associated with early culture positivity, indicating higher bacterial load.

Table 11: CRP Stratification and Pathogen Type

Table 11 categorizes pathogens based on CRP levels into mild, moderate, and severe response.

High CRP levels frequently corresponded to more virulent Gram-negative organisms.

Table 12: Correlation Coefficient Between CRP and Resistance Profile

Table 12 reports the strength of association between CRP and resistance traits.

There was a moderate to strong positive correlation between CRP levels and resistance profiles

Table 1 highlights the demographic profile of BSI patients, predominantly middle-aged males. Table 2 summarizes common clinical signs, with fever and tachycardia being prominent. Table 3 shows E. coli and Klebsiella as the most common pathogens. Table 4 confirms the predominance of Gram-negative isolates. Table 5 demonstrates significantly elevated CRP in Gram-negative infections. Table 6 reveals the frequency of MDR, ESBL, and MRSA strains. Table 7 links elevated CRP to MDR and ESBL infections, showing statistical significance. Table 8 indicates higher CRP levels with longer fever duration. Table 9 correlates infection source with CRP, showing higher values in respiratory and intra-abdominal infections. Table 10 suggests that higher CRP is associated with quicker culture positivity. Table 11 stratifies CRP levels with the likely organism type and virulence. Table 12 provides statistical evidence for moderate-to-strong correlation between CRP and resistance traits

Bloodstream infections (BSIs) continue to be a major cause of hospital admissions and complications in both critical care and general inpatient settings. Early detection of causative organisms and timely administration of effective antimicrobial therapy are essential for improving patient outcomes^[8]. However, the increasing prevalence of multidrug-resistant (MDR) organisms and delayed culture results often hinder appropriate management. In this context, inflammatory biomarkers such as C-reactive protein (CRP) can play an important adjunctive role in the early identification and stratification of infection severity^[9].

In the present study, Gram-negative bacteria were more frequently isolated from blood cultures than Gram-positive organisms. Escherichia coli and Klebsiella pneumoniae were the predominant pathogens among the Gram-negative group, while Staphylococcus aureus was the most common among Gram-positive isolates. The predominance of Gram-negative organisms in BSIs observed here reflects a typical pattern seen in nosocomial and urinary tract–associated infections, particularly in patients with catheters, underlying comorbidities, or recent hospitalizations^[9].

The mean CRP levels were significantly higher in patients with Gram-negative infections compared to those with Gram-positive infections. This difference suggests a more severe systemic inflammatory response associated with Gram-negative bacteremia. The higher CRP concentrations likely reflect the greater pro-inflammatory stimulus induced by lipopolysaccharides and endotoxins present in the outer membranes of Gram-negative bacteria. This physiological response results in accelerated hepatic synthesis of acute-phase proteins, including CRP, mediated through cytokine cascades^[10].

A considerable proportion of isolates in this study exhibited antibiotic resistance patterns, including MDR, ESBL production, and methicillin resistance. CRP levels were notably elevated in patients infected with MDR and ESBL-producing organisms^[11]. These observations suggest that infections caused by resistant organisms may provoke a more intense or prolonged inflammatory response, either due to delayed clearance of the pathogen or due to greater tissue damage inflicted by resistant strains. In contrast, patients infected with MRSA exhibited moderately elevated CRP levels, which, while higher than those in patients infected with sensitive strains, were still lower than those seen in MDR Gram-negative infections^[12].

The association between CRP levels and resistance profiles reinforces the potential role of CRP as a surrogate indicator for identifying high-risk infections. This is particularly valuable in clinical settings where immediate microbiological confirmation is unavailable. Elevated CRP values, especially in the context of Gram-negative sepsis or suspected drug-resistant infections, could prompt the early use of broader-spectrum antibiotics or escalation of care. Moreover, CRP stratification can assist clinicians in prioritizing patients for intensive monitoring or isolation protocols when multidrug-resistant pathogens are suspected^[13].

In addition to microbial factors, clinical parameters such as fever duration and site of infection were also associated with CRP levels. Patients with prolonged fever and those with respiratory or intra-abdominal sources of infection tended to have higher CRP values. This supports the understanding that CRP levels not only reflect microbial burden but also the extent and location of systemic inflammation. Faster culture positivity, observed in patients with higher CRP levels, may indicate a higher bacterial load, further supporting the role of CRP in reflecting disease intensity^[14].

Although CRP is a nonspecific biomarker and cannot distinguish among individual pathogens or resistance mechanisms, its quantitative correlation with Gram classification and resistance traits offers practical clinical utility. When used alongside clinical examination and basic laboratory data, CRP measurement can improve the precision of empirical treatment decisions while awaiting definitive culture and sensitivity reports^[15].

The present study highlights the feasibility of using CRP levels as a rapid, cost-effective adjunct in the early diagnosis and risk assessment of BSIs. It also emphasizes the importance of combining biomarker data with microbiological results for a more comprehensive understanding of infection dynamics. Despite its limitations such as the cross-sectional design and exclusion of other biomarkers this study underscores the diagnostic and prognostic relevance of CRP in bloodstream infections in hospital-based settings.

This study demonstrated a significant association between serum C-reactive protein (CRP) levels and the type of bacterial isolates, as well as their antibiotic resistance profiles, in patients with bloodstream infections. CRP levels were markedly higher in cases involving Gram-negative organisms and in infections caused by multidrug-resistant and ESBL-producing pathogens, suggesting a stronger inflammatory response in these groups.

The findings indicate that CRP, although nonspecific, may serve as a useful adjunctive biomarker for early risk stratification, particularly in settings where blood culture results are pending or delayed. CRP can aid in anticipating pathogen virulence and resistance potential, supporting more rational and timely decisions regarding empirical antimicrobial therapy.

Incorporating CRP measurements into the initial evaluation of patients with suspected sepsis may help identify those at greater risk of complications and antimicrobial resistance. While CRP cannot replace microbiological testing, its use alongside clinical judgment and culture results may enhance diagnostic accuracy and therapeutic planning in bloodstream infections.

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