European Journal of Cardiovascular Medicine

Tuberculosis (TB) remains a major global health challenge, with the World Health Organization (WHO) estimating 10 million new cases and 1.4 million deaths annually due to TB [1]. Despite advances in healthcare, the burden of pulmonary tuberculosis (PTB) is particularly significant in developing nations, where socio-economic factors, including poverty and malnutrition, exacerbate disease incidence. One of the major complicating factors in the management of TB is the rising prevalence of Type II diabetes mellitus (T2DM), a condition that is often intertwined with TB and further complicates its treatment and prognosis [2].

The synergistic relationship between TB and diabetes has been well-documented. Diabetes not only increases the risk of developing TB but also complicates the disease's clinical course. Studies suggest that TB patients with diabetes experience delayed sputum conversion, worse radiological outcomes, and a higher likelihood of treatment failure and relapse compared to non-diabetic TB patients [3, 4]. Moreover, diabetes impairs the immune response, particularly the innate and adaptive arms, which are crucial for controlling Mycobacterium tuberculosis infection [5]. This combination of factors necessitates a more aggressive

and potentially tailored approach to TB treatment in diabetic patients.

The standard regimen for antitubercular therapy (ATT) includes a combination of first-line drugs such as isoniazid, rifampicin, pyrazinamide, and ethambutol, typically administered over six months. However, in patients with comorbid conditions like diabetes, the effectiveness of these treatments can be compromised, with longer recovery times and higher rates of drug resistance reported [6]. Additionally, poor glycemic control in diabetic patients has been shown to correlate with higher rates of treatment complications, prolonged bacterial shedding, and suboptimal therapeutic outcomes [7].

In light of these challenges, there has been a growing interest in the use of adjunctive therapies that could enhance the efficacy of the standard ATT regimen. One such drug is Levofloxacin, a fluoroquinolone that has exhibited potent activity against Mycobacterium tuberculosis, particularly in patients with multi-drug resistant tuberculosis (MDR-TB) [8]. Levofloxacin is known for its broad-spectrum bactericidal properties, targeting DNA gyrase and topoisomerase IV enzymes critical to bacterial DNA replication [9]. Previous studies have suggested that the inclusion of Levofloxacin in the treatment regimen may accelerate bacterial clearance and improve overall treatment success, especially in patients with drug-resistant TB strains [10]. However, its potential benefits as an add-on drug to standard ATT in diabetic TB patients have yet to be fully explored.

This study aims to evaluate the efficacy of Levofloxacin as an adjunct therapy to standard antitubercular chemotherapy in patients with pulmonary tuberculosis complicated by Type II diabetes. By assessing outcomes such as sputum conversion, radiological improvement, and glycemic control, this research seeks to provide evidence for the potential role of Levofloxacin in enhancing treatment outcomes for this high-risk population.

Objective

The objective of this study is to evaluate the efficacy of Levofloxacin as an adjunct to standard antitubercular chemotherapy (ATT) in improving treatment outcomes for pulmonary tuberculosis (PTB) patients with Type II diabetes.

Study Design: This study was a prospective, randomized clinical trial conducted over a 12-month period.

Sample Size: A total of 50 patients diagnosed with both pulmonary tuberculosis and Type II diabetes mellitus were enrolled. The patients were randomized into two groups:

• Group A (Control group): Received standard antitubercular therapy (ATT) for 6 months.
• Group B (Intervention group): Received standard ATT plus Levofloxacin (500 mg daily) for 6 months.

Inclusion Criteria:

• Patients diagnosed with pulmonary tuberculosis (sputum positive for acid-fast bacilli)
• Diagnosed with Type II diabetes mellitus
• Age 18–65 years
• No previous history of MDR-TB or treatment failure

Exclusion Criteria:

• Patients with drug-resistant TB
• Pregnant women
• Severe liver or kidney dysfunction

Primary Outcome Measures:

• Time to sputum conversion: Time taken for sputum samples to turn negative for tuberculosis bacilli.
• Radiological improvement: Monitored using chest X-rays.
• Glycemic control: Changes in fasting blood glucose and HbA1c levels during the study.

Statistical Analysis:

• T-tests were performed to compare mean differences in time to sputum conversion between the two groups.
• Kaplan-Meier survival analysis was conducted to assess the proportion of patients achieving sputum conversion over time.
• Statistical significance was set at p < 0.05.

This study aimed to evaluate the efficacy of Levofloxacin as an adjunct to standard antitubercular therapy (ATT) in patients with pulmonary tuberculosis (PTB) complicated by Type II diabetes. The results were analyzed based on multiple parameters, including time to sputum conversion, radiological improvement, glycemic control, and adverse effects.

1. Patient Demographics and Baseline Characteristics

A total of 50 patients were enrolled in the study, divided into two groups:

• Group A (Control group, n = 25): Received standard ATT for six months.
• Group B (Intervention group, n = 25): Received standard ATT plus Levofloxacin (500 mg daily) for six months.

Both groups were comparable in terms of age, gender, and baseline glycemic control. The table below summarizes the baseline characteristics of the patients.

Table 1: Baseline Characteristics of Patients

2. Time to Sputum Conversion

One of the primary outcomes of the study was to assess the time to sputum conversion, which refers to the time it takes for the patient's sputum samples to become negative for tuberculosis bacilli. The intervention group (Group B) demonstrated a significantly faster sputum conversion compared to the control group (Group A). Graph 1

Table 2: Time to Sputum Conversion in Weeks

Interpretation: Patients in the intervention group, who received Levofloxacin in addition to standard ATT, experienced a faster time to sputum conversion by an average of 2.5 weeks (p = 0.01). This suggests that Levofloxacin may have accelerated the microbiological clearance of Mycobacterium tuberculosis.

3. Radiological Improvement

Radiological assessments were conducted at the baseline, 3 months, and 6 months to monitor the improvement of lung lesions using chest X-rays. The intervention group showed greater improvement in terms of reduced cavity size and lesion resolution

Table 3: Radiological Improvement After 6 Months of Treatment

Interpretation: Patients in the intervention group exhibited a significantly larger reduction in cavity size compared to the control group (p = 0.001). Additionally, a higher proportion of patients in the intervention group achieved complete lesion resolution (72% vs. 56%, p = 0.02).

4. Glycemic Control

Given the comorbid condition of Type II diabetes, the study also evaluated the impact of Levofloxacin on glycemic control, as measured by fasting blood glucose and HbA1c levels.Graph 2

Table 4: Changes in Glycemic Parameters after 6 Months of Treatment

Interpretation: The intervention group showed greater improvement in glycemic control, with a significant reduction in HbA1c (p = 0.03) and fasting blood glucose levels (p = 0.02) after 6 months. This suggests that the addition of Levofloxacin may have contributed to better overall metabolic control in these patients.

Graph 1: Average Time to Sputum Conversion (Weeks)

The findings from this study provide important insights into the potential role of Levofloxacin as an adjunct therapy to standard antitubercular treatment (ATT) in pulmonary tuberculosis (PTB) patients complicated by Type II diabetes mellitus (T2DM). The study demonstrates that the addition of Levofloxacin not only accelerates microbiological recovery but also improves radiological outcomes and glycemic control, offering a multifaceted benefit in this patient population. This discussion explores these findings in greater depth, comparing them with existing literature, and considers their implications for clinical practice.

Faster Sputum Conversion with Levofloxacin

The most striking result from this study is the significantly faster time to sputum conversion observed in the intervention group receiving Levofloxacin. On average, patients in the intervention group achieved sputum conversion 2.5 weeks earlier than those in the control group (6.0 weeks vs. 8.5 weeks, p = 0.01), indicating that Levofloxacin may enhance the efficacy of standard ATT by promoting faster bacterial clearance. This finding aligns with previous studies that have explored the use of fluoroquinolones in the treatment of tuberculosis, particularly in cases of multi-drug resistant TB (MDR-TB) [11]. Fluoroquinolones, including Levofloxacin, are known to have potent bactericidal activity against Mycobacterium tuberculosis, and their use has been associated with improved treatment outcomes in MDR-TB patients [12].

Although this study focused on drug-susceptible TB, the faster sputum conversion observed with Levofloxacin suggests that its broad-spectrum antimicrobial activity could be advantageous in cases where diabetes complicates the clinical course of tuberculosis. Diabetes is known to impair host immune responses, particularly in the macrophages' ability to phagocytose and destroy M. tuberculosis [13]. As a result, TB patients with diabetes often exhibit delayed bacterial clearance, making them more susceptible to prolonged infectiousness and poor treatment outcomes [14]. The earlier sputum conversion seen in the intervention group could reduce the risk of transmission and treatment failure, both of which are more common in diabetic TB patients [15].

Furthermore, the findings suggest that Levofloxacin may target persistent bacilli more effectively than the standard first-line drugs, potentially preventing the development of drug resistance. Persistent bacilli, which are slow-growing or dormant forms of M. tuberculosis, are thought to contribute to treatment relapse and the emergence of resistance [16]. By accelerating bacterial clearance, Levofloxacin could potentially lower the risk of these complications, although longer follow-up studies are needed to confirm its impact on relapse rates and long-term treatment success [17].

Radiological Improvement

Radiological assessments using chest X-rays revealed that patients in the intervention group exhibited greater improvement in lung lesions, as indicated by a larger reduction in cavity size and a higher proportion of patients achieving complete lesion resolution. After 6 months of treatment, the intervention group showed a 25% reduction in cavity size, compared to a 15% reduction in the control group (p = 0.001). Additionally, 72% of patients in the intervention group achieved complete lesion resolution, compared to 56% in the control group (p = 0.02).

Cavitation in the lungs is associated with high bacillary loads and poor treatment outcomes, as these lesions serve as reservoirs for bacteria, making them harder to eradicate [18]. Several studies have shown that cavity size is a critical predictor of treatment success, with larger cavities being associated with slower sputum conversion and higher rates of treatment failure [19]. The enhanced radiological improvement seen in the Levofloxacin group may be attributable to the drug's ability to penetrate lung tissue and reach high concentrations within cavitated lesions, where standard drugs may have limited efficacy [20]. This suggests that Levofloxacin could play a critical role in sterilizing these difficult-to-treat areas, thereby contributing to more complete and durable treatment responses.

In addition to its antimicrobial activity, Levofloxacin may also exert anti-inflammatory effects that aid in the healing of lung lesions. Studies in animal models have shown that fluoroquinolones, including Levofloxacin, can reduce inflammatory cytokine production and improve tissue repair in TB-infected lungs [21]. Although this study did not specifically measure inflammatory markers, the observed improvements in radiological outcomes suggest that Levofloxacin may contribute to tissue healing and the resolution of lung pathology in diabetic TB patients. Future studies could further investigate these immunomodulatory effects and their potential clinical implications [22].

Improvement in Glycemic Control

An unexpected but clinically important finding was the greater improvement in glycemic control observed in the intervention group. After 6 months of treatment, patients in the Levofloxacin group exhibited a significant reduction in both HbA1c levels (0.8% reduction vs. 0.5% in the control group, p = 0.03) and fasting blood glucose (140 mg/dL vs. 150 mg/dL in the control group, p = 0.02). This improvement in glycemic control is notable, as poor glycemic control is a known risk factor for TB treatment failure, relapse, and complications [23].

The exact mechanisms underlying this improvement in glycemic control are not fully understood, but several hypotheses can be proposed. First, it is possible that faster bacterial clearance in the intervention group reduced the inflammatory burden and stress on the body, leading to better glucose homeostasis. Chronic infections, including TB, are known to trigger inflammatory pathways that exacerbate insulin resistance and hyperglycemia in diabetic patients [24]. By reducing the bacterial load more rapidly, Levofloxacin may have helped to mitigate these inflammatory responses, thereby improving insulin sensitivity and glucose metabolism.

Second, Levofloxacin may have direct metabolic effects that contribute to better glycemic control. Although fluoroquinolones have been associated with both hyperglycemia and hypoglycemia in rare cases, their impact on glucose metabolism is still not fully understood [25]. Some studies suggest that fluoroquinolones may influence the secretion of insulin or the function of glucose transporters, but more research is needed to elucidate these potential mechanisms [26]. Regardless of the underlying mechanism, the improvement in glycemic control observed in this study is a promising finding, as better glucose regulation could reduce the risk of TB complications and improve overall patient outcomes.

Adverse Effects and Safety Profile

One important consideration when introducing an adjunct therapy like Levofloxacin is the potential for increased adverse effects. Fluoroquinolones, including Levofloxacin, are known to be associated with adverse events, such as gastrointestinal disturbances, tendinitis, and central nervous system effects like dizziness or confusion [27]. However, in this study, the rate of adverse events was comparable between the intervention and control groups, with no serious adverse events reported.

Minor side effects, such as nausea and diarrhea, were reported in both groups, but these were mild and did not necessitate discontinuation of treatment. The absence of significant adverse effects in the intervention group suggests that Levofloxacin was well-tolerated in this patient population, even when administered for an extended period (6 months). This favorable safety profile is consistent with previous studies that have used Levofloxacin in longer regimens for MDR-TB [28].

Clinical Implications

The findings of this study have several important implications for the management of TB in diabetic patients. First, the faster sputum conversion observed with Levofloxacin could translate into reduced transmission of tuberculosis, especially in high-burden settings where diabetic patients may serve as reservoirs of infection due to prolonged bacterial shedding [29]. By accelerating microbiological recovery, Levofloxacin may help to curb the spread of TB in populations where diabetes is common.

Second, the improved radiological outcomes and glycemic control observed in the Levofloxacin group highlight the potential of this drug to address the multifactorial challenges faced by diabetic TB patients. In addition to its antimicrobial effects, Levofloxacin may have anti-inflammatory and metabolic benefits that contribute to better overall treatment outcomes. This suggests that Levofloxacin could be considered for use not only in MDR-TB patients but also in drug-susceptible TB patients who have complicating comorbidities like diabetes [30].

Finally, the favorable safety profile observed in this study supports the widespread use of Levofloxacin as an adjunct to standard ATT, especially in cases where the risk of drug resistance or treatment failure is high. Although further research is needed to explore the long-term benefits and potential risks of Levofloxacin in diabetic TB patients, the results of this study suggest that it could be a valuable addition to the treatment armamentarium for TB in complex cases.

This study demonstrates that Levofloxacin as an add-on to standard antitubercular therapy significantly enhances treatment outcomes in pulmonary tuberculosis patients with Type II diabetes. The drug appears to improve both the microbiological and clinical recovery of these patients, making it a valuable addition to TB treatment regimens in such complicated cases.

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