Understanding the role of Doxycycline in Management of Infections in Daily Medical Practice
Doxycycline is a broad-spectrum antimicrobial agent with activity against gram-positive, gram-negative, atypical bacteria as well as some protozoan pathogens such as malaria. Doxycycline is an asset to developing countries like India as it is a cost-effective antimicrobial agent. With promising susceptibility data recently published against almost a dozen common pathogens, Doxycycline remains a drug of choice for treating many infectious diseases.[1] The scope and evidence of Doxycycline across specific commonly encountered infections in Indian practice settings is reviewed to facilitate clinicians make a rational choice.
Doxycycline: Rapid Efficacy Respiratory Infections: Large Primary Care Settings' Study
Pestel published a large multicentre trial, studying the efficacy of Doxycycline in respiratory tract infections encountered in primary care settings. About 1,740 patients across different age groups from 6-80 years were included. The most common diagnosis was acute bronchitis or acute exacerbations of chronic bronchitis. The rest comprised of bronchopneumonia, tonsillitis, sinusitis, etc. The antimicrobial intervention was only Doxycycline 200 mg/day for up to 10 days.
The results showed that about 87% of patients achieved good clinical results with doxycycline treatment. Clinical improvement was noted in 72% of patients by day 3. The clinical assessment reported rapid improvement in fever, cough, the volume of expectoration, and pain associated with respiratory tract infections within 3-5 days. The study concluded that treatment with Doxycycline was highly efficacious and led to rapid clinical recovery in primary care settings [2]
Anti-Inflammatory Action of Doxycycline Benefits COPD Patients: Indian Experience
An Indian study published by Dalvi et al was aimed to assess the effect of 4 weeks of doxycycline 100 mg once daily among patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) with stable symptoms. It was an interventional, randomized, observer-masked, parallel study, including 61 patients. Lung function and C- Reactive Protein (CRP) levels were assessed before and after treatment.
At 4 weeks, mean forced expiratory volume (FEV1) increased significantly by 153 ml in doxycycline group (P < 0.001) and decreased by 33 ml in the control group. There was a significant difference in mean change in FEV1% predicted, Forced vital capacity (FVC), and FVC % predicted among both groups. The mean reduction in baseline serum CRP was 45.59% and 15.78% in doxycycline and standard care group, respectively. These results demonstrated that pulmonary functions significantly improved in doxycycline group and mean reduction in baseline serum C- Reactive Protein (CRP) was significantly greater in the doxycycline group as compared to standard care. The study concluded that the anti-inflammatory and matrix metalloproteinases (MMP) blocking property of doxycycline may be responsible for improvement in lung function and disease activity markers in this population[3]
Doxycycline Leads to Better Results in Acne: South Asian Study
Ghafoor et al published a study aimed to compare the efficacy of oral azithromycin with oral doxycycline in the treatment of moderate acne vulgaris in the South Asian population. Three hundred and eighty-six adolescents and adults (aged 14–30 years) suffering from moderate acne vulgaris on the face were included in the study. Patients were treated with either azithromycin 500 mg daily for 4 consecutive days monthly or doxycycline 100 mg daily for 3 months.
Efficacy was assessed based on the disappearance of lesions - whiteheads, blackheads, red spots, and red bumps, and it was measured in terms of improvement in percentages - Excellent (100%), Good (80–90%), Moderate (50–79%), Mild (30–49%), and No Response (<30%).
The results reported an excellent response in 3.1% and a good response in 22.8% of patients treated with azithromycin. While in the doxycycline group, 11.4% had excellent and 55.4% of patients had a good response, the inter-group difference being statistically significant. The study concluded doxycycline as a better option for treatment of acne vulgaris over azithromycin[4]
Doxycycline for Chemoprophylaxis against Malaria
Among tetracyclines, doxycycline is the only recommended prophylactic agent against malaria[5]. Doxycycline was approved for this indication by the FDA (Food and Drug Administration) nearly three and a half decades after its development – a testimony that this antimicrobial agent has often stood the test of time. In multidrug resistance zones, doxycycline is used as malaria chemoprophylaxis against P. falciparum at a dose of 100 mg/day starting at the day of arrival in endemic areas and continuing for up to 4 weeks after returning. The primary efficacy and safety studies of doxycycline prophylaxis have been successfully conducted with different population groups living in endemic areas across eleven countries in Asia and Africa[6].
Doxycycline Improves Mortality in Dengue Patients
Terry M et al conducted a study on 231 dengue hemorrhagic fever patients. The patients were randomized to receive either standard care or oral doxycycline 100 mg twice daily for a week in addition to standard care. The results showed that the Doxycycline treated group presented a 46% lower mortality than that observed in the untreated group (p=0.05). Besides, administration of doxycycline resulted in a significant decrease in tumor necrosis factor (TNF) & IL-6 (interleukin 6) levels compared to standard care during follow-up at day 3, day 5, and day 7 (p<0.01). Mortality in both groups was consistently associated with higher levels of TNF and IL-6 (p<0.01) compared to those who survived, at each time point. The study concluded doxycycline could improve clinical and mortality outcomes among dengue patients and this effect could be mediated by decreasing pro-inflammatory cytokine levels.[7]
Doxycycline in Leptospirosis Chemoprophylaxis
Leptospirosis is an acute anthropo-zoonotic infection encountered in many countries globally. It is caused by spirochaete Leptospira interrogans which has 23 serogroups and more than 200 serotypes. Leptospirosis has varied clinical presentations frequently mimicking other illnesses, often leading to misdiagnosis or under-diagnosis. The spectrum of disease may range from mild infection to life-threatening pulmonary and renal complications and reported case fatality may go up to 20%. Guidelines cite Doxycycline as a drug of choice for chemoprophylaxis and Penicillins as a preference for treatment[8]
The Indian National Guidelines for Diagnosis, Case Management Prevention and Control of Leptospirosis recommend Doxycycline 100 mg twice a day for seven days for management of adults (non-pregnant and non-lactating) with clinically suspected Leptospirosis. [9]
Take-Home Message for Clinicians
Doxycycline is a broad-spectrum antibiotic that has only further extended its therapeutic potential through its anti-inflammatory & immunomodulatory properties re-discovered from time to time. Its microbiological profile and pleiotropic activities have made the use of doxycycline clinically relevant in primary care settings.
As durable evidence continues to accumulate over time favoring doxycycline inclusive of Indian data, it retains its place among the global authorities and various national guidelines.
It is noteworthy that in the latest Indian Council of Medical Research (ICMR) treatment guidelines for Antimicrobial Use in Common Syndromes [10], it has been cited under the section for the 'management of acute fevers', that empirical treatment with doxycycline for patients with undifferentiated fever and negative rapid diagnostic tests for malaria and dengue is an option for the clinician.
Thus, Doxycycline certainly remains a clinician's valuable choice for the treatment of specific infections, frequently encountered among Indian patients.
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Doxycycline, click HERE
References
Adapted from
[1] Mehta S, Susceptibility Pattern of Doxycycline in Comparison to Azithromycin, Cefuroxime, and Amoxicillin against Common Isolates: A Retrospective Study Based on Diagnostic Laboratory Data, Journal of The Association of Physicians of India 2020;68:59-63
[2] M Pestel, Doxycycline in the treatment of respiratory tract infections, Chemotherapy 1975;21(1):91-108
[3] Dalvi PS, Singh A, Trivedi HR, Ghanchi FD, Parmar DM, Mistry SD. Effect of doxycycline in patients of moderate to severe chronic obstructive pulmonary disease with stable symptoms. Ann Thorac Med 2011;6:221-
[4] Ghafoor Ullah et al, Comparison Of Oral Azithromycin With Oral Doxycycline In The Treatment Of Acne Vulgaris, J Ayub Med Coll Abbottabad 2014;26(1):64-67
[5] Willerson D Jr, Rieckmann KH, Carson PE, Frischer H. Effects of minocycline against chloroquine-resistant falciparum malaria. Am J Trop Med Hyg. 1972;21:857–62.
[6] Gaillard et al, Tetracyclines in malaria, Malar J (2015) 14:445 DOI 10.1186/s12936-015-0980-0
[7] Terry M Fredeking et al, Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to
a Reduction in IL-6 and TNF Levels, Recent Patents on Anti-Infective Drug Discovery 2015; 10(1):51-58
[8] Jaykaran Charan et al, Prophylaxis and Treatment for Leptospirosis: Where are the Evidence?, National Journal of Physiology, Pharmacy & Pharmacology 2012; 2(2): 78-83
[9] Prasad J et al, The Indian National Guidelines for Diagnosis, Case Management Prevention and Control of Leptospirosis 2015:1-18
[10] Treatment Guidelines for Antimicrobial Use in Common Syndromes, Indian Council of Medical Research 2019, 2ND Edition, Pages 1-26
