Severe pneumonia is a critical respiratory disorder commonly encountered in the intensive care unit (ICU), characterized by rapid onset, swift progression, and a notably high mortality rate (1). The geriatric population, owing to their inherently compromised immune systems and diminished respiratory functions, is particularly vulnerable to this life-threatening condition. The pathophysiological mechanisms underlying severe pneumonia in the elderly patients are complex, involving a dysregulated immune response, impaired mucociliary clearance, and reduced pulmonary reserve capacity (2, 3). This finding not only predisposes them to initial infection but also contributes to the development of severe complications such as septic shock and acute respiratory distress syndrome (ARDS) (4).

Historically, the treatment paradigm for severe pneumonia has predominantly relied on empirical antibiotic therapy (5). However, the overuse of antibiotics has contributed to the emergence of antimicrobial resistance (AMR), a major public health concern associated with prolonged hospitalization, increased healthcare costs, and elevated mortality (6). In the context of severe pneumonia in the elderly, the presence of multiple comorbidities further exacerbates the challenges associated with AMR, as these patients often require extended antibiotic courses and are more likely to experience treatment failures (7).

Procalcitonin (PCT), a 116-amino-acid glycoprotein, has emerged as a promising biomarker in the management of severe infections, including severe pneumonia (8). In healthy individuals, PCT is produced at minimal levels, but during severe bacterial infections—particularly sepsis—its expression is markedly upregulated through inflammatory activation (9). This upregulation occurs in response to pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) (10, 11).

The elevation of serum PCT levels in patients with severe pneumonia is not only a diagnostic indicator but also has prognostic implications. Higher PCT levels have been associated with more severe disease phenotypes, including an increased risk of septic shock, ARDS, and mortality (12). Furthermore, dynamic monitoring of PCT levels offers valuable insight into treatment response: a decline in PCT generally indicates a favorable response to antibiotics, whereas persistently elevated or rising levels may suggest treatment failure or antimicrobial resistance (13).

Despite its established utility in general populations, evidence on PCT-guided therapy specifically in elderly ICU patients with severe pneumonia remains limited. Physiological changes related to aging—such as altered immune reactivity, impaired organ function, and polypharmacy—may influence PCT kinetics and interpretability. Therefore, this study aims to address this gap by evaluating the clinical impact and biomarker dynamics of PCT-guided antibiotic therapy in elderly ICU patients with severe pneumonia.

Severe pneumonia is a major cause of morbidity and mortality in the ICU, with a fatality rate surpassed only by cardiovascular and neoplastic diseases. In the elderly population, the situation is even more critical due to their weakened physiological functions and the higher prevalence of comorbidities (15). This study aimed to explore the role of procalcitonin (PCT) dynamics in guiding antibiotic therapy for severe pneumonia in elderly ICU patients, and the results offer valuable insights.

In this study, we found that monitoring PCT dynamics may provide important guidance for antibiotic therapy in elderly patients with severe pneumonia. PCT, a precursor peptide of calcitonin, is present at extremely low levels in healthy individuals (usually < 0.1 μg/L). However, in cases of severe infection, such as severe pneumonia, its levels increase significantly. This increase is closely associated with the degree of inflammatory response (1).

Our results showed that, in the observation group, where antibiotic use was guided by PCT levels, treatment outcomes were generally more favorable compared to the control group that received conventional empirical antibiotic therapy. The PCT cutoff values used in this study (0.25 μg/L and 0.5 μg/L) were selected based on established international recommendations and previous clinical trials in critically ill populations (16), which have demonstrated both safety and efficacy in guiding antibiotic stewardship. These thresholds were further validated in our elderly cohort through sensitivity analyses. When PCT was > 0.5 μg/L, intensifying antibiotic treatment in the observation group seemed to effectively target ongoing severe infection. This is likely because a high PCT level indicates a significant bacterial load or a strong inflammatory reaction, and more aggressive antibiotic therapy can better control the infection. When PCT was ≥ 0.25 μg/L, continuing the antibiotic treatment appeared to help maintain pathogen suppression. On the other hand, when PCT was < 0.25 μg/L, discontinuing antibiotics in combination with clinical assessment was associated with reduced unnecessary exposure and a potentially lower risk of antibiotic-related complications, including resistance and secondary infections (17). These observations are generally in line with previous research, which has suggested that PCT-guided antibiotic therapy may support more rational treatment strategies and be associated with improved outcomes (17, 18); however, definitive conclusions should be confirmed in future prospective studies.

Compared to traditional diagnostic methods, PCT has distinct advantages. Chest imaging and routine biochemical tests lack specificity in diagnosing the cause of severe pneumonia. For example, chest X-rays or CT scans may show infiltrates, but it is difficult to determine whether the cause is bacterial, viral, or fungal. Routine biochemical markers such as white blood cell count (WBC) and C-reactive protein (CRP) can be elevated in various inflammatory conditions and do not specifically indicate bacterial infection (19). In contrast, PCT is more specific to severe bacterial infections. Although pathogen detection remains the gold standard for identifying the causative agent, it has limitations such as long detection times and low positive detection rates, which often delay the initiation of targeted treatment. PCT, with its rapid and reliable detection, may help address this gap and support clinicians in making more timely treatment decisions.

Regarding inflammatory markers, we focused on IL-6 in combination with PCT because IL-6 plays a well-established role as a key mediator of the acute inflammatory response in bacterial pneumonia and correlates strongly with disease severity and clinical outcomes. While we acknowledge that a broader cytokine panel (e.g., IL-1β, TNF-α, and IL-10) could provide additional immunological insights, our aim was to identify clinically tractable, widely available biomarkers to support rapid decision-making in the ICU setting (20, 21).

Elderly patients with severe pneumonia are a vulnerable group. They have a higher incidence of severe pneumonia due to factors such as weakened immune systems, multiple underlying diseases, and decreased lung function. The complexity and diversity of pathogens in this population further complicate treatment. In our study, PCT-guided antibiotic therapy was associated with more individualized antibiotic use in elderly patients. Adjusting treatment based on PCT levels appeared to improve infection control while potentially reducing the risks associated with inappropriate antibiotic use, including both overuse and underuse. The overuse of antibiotics may disrupt normal flora, increasing the risk of opportunistic infections (e.g., Clostridioides difficile) and promoting resistance, whereas their underuse may contribute to treatment failure and disease progression (22). Overall, PCT-guided therapy may help achieve a balance, promoting more appropriate antibiotic use without causing excessive harm (23).

Although this study has its own unique focus on elderly ICU patients with severe pneumonia, it is generally consistent with previous research suggesting that PCT may serve as a useful biomarker to guide antibiotic therapy (24, 25). In our study, PCT-guided therapy was associated with more individualized antibiotic use and rational treatment decisions. However, it should be noted that different studies may have slightly different PCT cutoff values for guiding antibiotic use, which may be due to differences in patient populations, study designs, or detection methods.

Despite its valuable findings, this study also has several limitations. As a single-center retrospective study, selection bias is possible, and generalizability to other ICU settings or patient populations is limited. Antibiotic regimens were not strictly standardized and may have been influenced by physician preference, thereby introducing potential treatment bias, and unmeasured confounding factors—such as frailty, comorbidities not captured in the dataset, or prior healthcare exposure—could also have affected outcomes. Importantly, mortality data, a key clinical endpoint in elderly ICU pneumonia, were not collected, limiting the clinical impact of our findings. In addition, the PCT cutoff values used for guiding antibiotic therapy (PCT > 0.5 μg/L for intensifying treatment, PCT ≥ 0.25 μg/L for continuing treatment, and PCT < 0.25 μg/L for discontinuation) were based on commonly accepted thresholds (16, 25) but may not be optimal for all elderly patients, particularly those with different underlying conditions or degrees of immunosuppression, and future studies should aim to refine these thresholds. Finally, the combined application of PCT with other indicators (e.g., WBC, CRP, and IL-6) (26) and clinical factors such as age, comorbidities, and response to initial treatment may allow for a more comprehensive assessment and support individualized antibiotic strategies, but prospective multicenter studies with hard endpoints are needed to validate this approach.

In conclusion, this retrospective study suggests the significance of PCT dynamics in guiding antibiotic therapy for severe pneumonia in elderly ICU patients, indicating that PCT-guided therapy may contribute to optimizing treatment and improving outcomes. However, this study has several limitations, including its retrospective design, the application of predetermined PCT cutoff values, and a restricted assessment of inflammatory biomarkers. Future large-scale, multicenter studies are warranted to validate these findings and investigate the integration of PCT with other indicators to construct more accurate models, with the ultimate goal of reducing the high mortality rate in this population.