Following its discovery, tetracycline (1948) was for several years one of the major antibiotics used in the treatment of acute respiratory tract infections. More recently its use has been declining partly due to the introduction of other agents such as ampicillin and co-trimoxazole,  and partly due to the emergence of tetracycline resistant strains of beta-haemolytic Streptococcus,, ,  Streptococcus pneumoniaela.,  and Haemophilus influenzae
Because of the activity of doxycycline against tetracycline resistant staphylococci, his study was designed to evaluate the use of doxycycline in lower respiratory tract infections.
(A) Criteria for Eligibility
The study was restricted to patients:
(1) Aged-12 years and above.
(2) With newly diagnosed, clinically active, lower respiratory tract infections with a radiological lesion.
(3) Who had had no . previous treatment what so ever during the present episode.
(4) Who were judged to be normally co-operative, and expected to be present at their address for at least one month, so that it was possible to arrange drug administration under supervision and subsequent follow up at (a) the chest clinic, University Health Centre and (b) the Chest O.P.D., University Hospital, Banaras Hindu University.
(1) Those who were pregnant.
(2) Those who had history of hypersensitivity to tetracycline.
(3) Those who were taking barbiturates or phenytoin as these drugs cause reduction in the half-life of doxycycline to approximately 7 hours., 
(1) Sputum for culture and sensitivity for secondary organisms. These tests were performed before and at the end of treatment.
(2) Total and differential leucocytic count and E.S.R.
(3) X-ray chest before and after the therapy.
(4) Liver and renal functions.
(D) Drug dosage
Doxycycline capsules (100 mg), 1 cap. 12 hrly. for two days followed by 1 cap. daily for 6 days. Duration of treatment was 8 days.
(1) Patients were assessed as per the following parameters:
(i) Cough with or without expectoration,
(ii) Amount of sputum, its colour and odour.
(iv) Chest pain.
(v) Associated upper respiratory tract infections.
(2) Clinical improvement was judged and classified as:
(a) Good: Complete disappearance of symptoms, physical signs and complete clearing of radiological lesion.
(b) Moderate: Disappearance of symptoms with persistence of some physical signs and partial clearing of radiological shadow.
(n) Poor: Persistence of symptoms, physical signs and no improvement radiologically.
Total number of patients admitted to this study were 82. Thirteen were excluded due to non-co-operation. Sixtynine patients were analysed at the end of the trial.
There were 47 males and 22 females with a M: F ratio of 2.1: 1. There were 6 patients belonging to the age group of 12 to - 20 years, 36 patients belonging to the age group of 20 to 40 years, 19 patients in the age group of 40 to 60 years and only 8 patients were above 60, years of age. The average age in the present series was 34.7 years.
This is presented in [Table 1].
Bacteriological status [Table 2]
The pathogens isolated were mostly Klebsiella pneumoniae (43.5%), Haemophilus influenzae (24.6%) and E. Coli (13%). Bacteria did not grow in an appreciable number of cases (15.9%). Streptococcus and Staphylococcus (Coagulase Negative and Positive) were usually isolated (18.8% and 11.6% respectively). In most of the cases (44), more than one pathogen were grown except when Klebsiella pneumoniae was alone isolated in 14 cases.
Sensitivity: Twenty-two patients were resistant to tetracycline and 36 were sensitive to it. No pathogens were grown in 11 cases.
Fortysix patients (66.7%) showed clinical success in that they showed complete disappearance of symptoms and physical signs at the end of treatment and started improving after 48 hours of treatment and maintained good health upto their following up visit. Radiological clearance was marked at the end of treatment. Sixteen patients (23.2%) were considered to be having partial success (moderate improvement) because they made satisfactory response during the treatment period and were symptom-free at the end of treatment but variable physical signs were present and later, during the follow-up they needed supportive therapy. Nine (13%) cases in this group needed further antibotic treatment for the return of some of the symptoms, though of minor nature.
Seven patients (l0.l%) neither improved clinically nor symptomatically and were labelled as failures. These patients did show mild to moderate relief of symptoms during the period of treatment but they were never asymptomatic and were mostly above 60 years of age who did show the organisms resistant to tetracyclines [Table 3].
(e) Toxicity: Not a single patient had any of the toxic manifestation even of minor nature.
(f) Tolerability: All patients tolerated doxycycline well and completed the treatment up to the end, probably due to the infrequent dosage schedule and well acceptance.
(g) Side effects: Four patients (5.8%) complained of nausea and vomiting of mild nature. In our experience if the vomiting was delayed for half an hour, enough of the drug will be absorbed to effect a cure,  Vomiting was usually prevented when capsules were taken with a glass of milk., 
Doxycycline has a wide range of antimicrobial activity against Gram positive and Gram negative bacterial. In a daily dose of 100 mg., it exerts a negligible impact on the intestinal flora as it is excreted in faeces (upto 90 %) , , ,  as an inactive conjugate or perhaps as a chelate. Though primarily it is bacteriostatic, in high concentration it is frequently bactericidal. In general, in vivo and in vitro efficacies closely parallel each other. Since the half life of doxycycline is long (17-20 hrs) and it is well absorbed, it is administered in lower daily dosage by oral route. Plasma concentrations are equivalent when doxycycline is given by oral or parenteral route., ,  Food does not interfere with the absorption of doxycycline like other groups of tetracyclines.,  It is not excreted in the urine to the same extent as other tetracyclines and does not accumulate in blood of patients with renal -failure7 hence is the safest among tetracyclines.
Although the penetrating rates of doxycycline are different in each bronchioles depending upon the inflammatory stage of the bronchioles, the transport rate of doxycycline to the respiratory tract is 15-25% and is much higher in comparison to other antibiotics (0.1-2% with pencillin, 1-3% with cephalosporins)., , 
Aitchison et al conducted a double blind trial to compare the efficacy of oral doxycycline and ampicillin in the treatment of acute and chronic bronchitis.
Dalal et al conducted a double blind trial of doxycycline and ampicillin in the treatment of acute and chronic bronchitis and showed that both drugs were equally effective.
Walker and James evaluated the efficacy of cephalexin (500 mg. 6 hourly for 10 days) and doxycycline (200 mg. 1st day and 100 mg. daily thereafter) in the treatment of lower respiratory tract infections in chronic obstructive pulmonary diseases. There was no significant difference.
Scott and West and Jacobs and Robinson showed better response with doxycycline (95%) when compared to ampicillin (87%) and sulfalen (76%) in lower respiratory tract infections.
When assessing the efficacy of a drug in acute respiratory infections it is the final assessment which is of importance to the clinician. Considering this view our success was 89.9% at the end of one month's follow up though 66.7% showed excellent improvement at the end of the treatment. The failures were due to mostly infections in the elderly people who have frequently been treated with antibiotics previously and yielded Pseudomonas and Staphylococci (coagulase + ve) infection on culture and were resistant to tetracycline. Doxycycline was not effective against Pseudomonas infection though it eliminated Staphylococci in 2 cases and was not effective in 2 cases.
Although 22 patients, (31.9%) were resistant to tetracycline, only 15 (21.8%) responded to doxycycline and 10.1% did have cross resistance to it. Thus it was effective in (68.2%) cases of resistant strains.
Doxycycline rapidly eliminated infections caused by Klebsiella pneumoniae, H. influenzae, Streptococcus and E. Coli. The toxicity was conspicuous by its absence and side effects were minimal which could be avoided by taking the capsule, after milk or light diet.
Doxycycline is effective (89.9%) in the treatment of lower respiratory tract infections and can be used in tetracycline resistant cases because of its minimum side effects, absence of toxicity and lower dosage schedule.
We are grateful to Mr. D. C. Mishra, District Sales Officer, M/s Ethico for supplying doxycycline for this trial. We are thankful to the entire staff of the B.H.U. Health Centre for their cooperation and in particular to the Health Visitor and Social Workers for day to day management of the patients. We are thankful to Prof. P. C. Sen, Head, Department of Microbiology, for undertaking the bacteriological assessments.