Hiremath Shobha Rani. R 1 , Mathai. S 1 , Pradeep. G 1 , Nagaraj. E.R 2 & Sathish. H.S 2

1. STUDY OF USE OF ANTIBIOTICS IN THE TREATMENT OF ACUTE SUPPURATIVE OTITIS MEDIA IN A TERTIARY CARE SETUP Hiremath Shobha Rani. R1, Mathai. S1, Pradeep. G1, Nagaraj. E.R2 & Sathish. H.S2 1.Dept. of Pharmacy Practice, Al – Ameen College of Pharmacy, Hosur Road, Bangalore – 560 027. 2. Bangalore Medical College, Bangalore – 560 001.

2. Abstract Problem Statement: Inappropriate antimicrobial use can lead to emergence of bacterial resistance. In India, the problem of antimicrobial resistance is very high due to factors such as improper prescribing/dosing and easy access to antibiotics over the counter. Management of resistance requires frequent and systematic review of antimicrobial susceptibility testing and rational drug use by way of appropriate guidelines. Objectives: To assess the extent of antibiotic usage in Acute Suppurative Otitis Media (ASOM) at a Government Tertiary Care hospital; to evaluate the antibacterial sensitivity pattern to the antibiotics used in the same; and to prepare guidelines for the use of antibiotics. Design: Prospective, randomized open study. Setting and Population: 1100 bed tertiary care government hospital in urban Bangalore. Study Population: 100 consecutive outpatients of the ENT Department with a diagnosis of ASOM formed the study sample. Intervention: Patient prescription analysis was carried out to assess the type and extent of antibiotics used. Middle ear pus specimens of the patients were taken and processed in the Microbiology department for identification of the organism, followed by sensitivity testing to antibiotics. Outcome Measures: Type of antibiotics used; identification of the organisms; and sensitivity pattern. Results: From the prescription analysis of 100 patients, it was found that Amoxicillin was the drug most widely prescribed, followed by Roxithromycin, Ciprofloxacin, Co-trimoxazole, Doxycycline, Cefuroxime, Azithromycin, Sparfloxacin and Ofloxacin (in descending order). Maximum antibiotic usage was found in the age group of 1-13 yrs. Identification of bacterial isolates was obtained from 86 cultures while the remaining 14 were sterile. The most predominant organism isolated were S. aureus (45 cases) followed by K.pneumoniae (14 cases) and P. aeruginosa (21 cases). In 6 cases mixture of organisms were also seen. The descending order of sensitivity of organism to antibiotics is: Amikacin>Ciprofloxacin>Gentamicin>Norfloxacin>Cefotaxime>Chloramphenicol>Co-trimoxazole>Cephalexin> Erythromycin>Penicillin>Ampicillin/Amoxicillin. Guidelines were prepared based on the findings and submitted to the ENT department. Conclusions: There is very poor correlation between the antibiotics prescribed and their sensitivity patterns as is clearly seen in the case of Amoxicillin, which continues to be most prescribed though most of the organisms found in the middle ear specimen are resistant to it. Sensitivity testing is thus necessary to prevent treatment failures. The guidelines have a major role to play in ensuring rational use of antibiotics during treatment of ASOM.

3. Introduction Suppurative Otitis Media(ASOM) refers to a clinically identifiable bacterial infection of the middle ear and is usually treated with antibiotics.  Otitis media has been identified as one of the most frequent reasons for outpatient antibiotic therapy and the widespread use of antibiotics to treat Otitis Media has resulted in an alarming increase in antibiotic-resistance of the bacterial strains that cause the same. In most cases, the causative organism is not isolated before treatment is initiated and the choice of antibiotics is based on the efficacy against the most common pathogens reported in published studies. The function of sensitivity testing is to guide the choice of treatment in individual patient and to provide surveillance data to monitor resistance trend. Along with the study of national or international trends of resistance for any disease, it is important to gather local information on resistance to form policies /guidelines in individual localities.

4. AIM To evaluate the rationale of antibiotic usage in the treatment of Acute Suppurative Otitis Media , at Victoria Hospital • OBJECTIVES • To assess the antibiotics prescribed for ASOM in the ENT Department of Victoria Hospital. • To evaluate the anti bacterial sensitivity pattern to the antibiotics used. • To prepare guidelines for the use of Antibiotics in ASOM in the ENT Department of Victoria Hospital.

5. Methods Study Site: ENT Department of Victoria Hospital (1100 bedded tertiary care hospital in Bangalore) Study Sample: Consecutive 100 outpatients of the ENT Dept with a diagnosis of Acute Suppurative Otitis Media. Inclusion Criteria:Outpatients - both pediatric and adult population with Acute Suppurative Otitis Media. Exclusion Criteria: Outpatients - with only ear pain & no ear discharge and patients who were on antibiotics (oral/parenteral/local application) at least two weeks before his/her visit to the hospital.

6. Methodology A detailed patient history was taken and recorded. Pus specimens were taken with the help of sterile cotton wool ear swabs by ENT doctor from the infected ear of the patients. The samples were processed in the department of microbiology, Victoria Hospital. One swab was used for Gram stain and the other swabs were inoculated into different media namely Chocolate agar, Blood agar & Mac Conkeys Agar. After inoculation the media were incubated at 370 C for 12-48 hrs. Once the colony appears identification of the colony is done by standard biochemical tests. Antibiotic Sensitivity Testing: After isolation of the individual organism, it was tested for antibiotic sensitivity by disk diffusion method. Based on the extent of the zone of inhibition, the sensitivity pattern of the particular organism to the antibiotic was determined.

7. Results The patient’s age ranged from 3 months to 85 yrs. 62% of the patients were in the age group of 1-13 yrs, 7% in the age group of 13-18 yrs and 31% in the adult group. 54% of the patients belonged to lower economic group whereas 46% belonged to the middle economic group. Symptoms of Acute Otitis Media in 100 patients

8. The antibiotics prescribed in the hospital were listed from the prescription analysis of 100 patients before the culture sensitivity test and are shown in Figure 01. Figure 01: Usage of antibiotics

9. From the analysis of pus specimens of the patients, bacterial isolates were obtained from cultures in 86 cases whereas the cultures were sterile in the remaining 14 cases. Results of the bacterial cultures are shown in Figure 02. Figure 02: Bacterial cultures of patients The most predominant organisms isolated were S.aureus (45%) followed by K. pneumoniae(14%) and P.aeruginosa (8%). Mixture of organisms were also seen (6%). Most of the isolates were seen in children (1-13yrs) followed by adults (18-60yrs). Mixture of organisms were more seen in age group of 1-13yrs.

10. The sensitivity pattern of all the isolated organisms are shown in Figure 03. Figure 03: Sensitivity pattern of isolated organism No. of isolates sensitive to antibiotics Sensitivity testing was based on the antibiotic discs available in the microbiology department. Hence, all the antibiotics prescribed were not tested.

11. Summary • In the hospital, Amoxicillin remains the drug of choice, which is in accordance with STGs. It is also the most commonly prescribed drug in the hospital. • However, from the culture sensitivity test it has been found that most of the organisms are resistant to Amoxicillin which may be attributed to the rampant misuse of the drug leading to treatment failures. • Amoxicillin/Clavulanate may be used as the next choice for treating ASOM, in case of resistance to amoxicillin. • In case of patients allergic to beta lactam antibiotics, Cotrimoxazole or Erythromycin or Azithromycin can be used. • Although the organisms are most sensitive to Amikacin, it is not recommended, as ototoxicity is one of the primary adverse effects associated with Amikacin therapy. • Although Gentamicin ear drops are being prescribed for ASOM, it is not appropriate due to its ototoxicity.

12. As the organisms were found to be sensitive to fluoroquinolones, prescribing ciprofloxacin may be considered in adult patients only; as safety and efficacy of fluoroquinolones, in children and adolescents under age 18 have not been established. • The organisms are found to be highly sensitive to Cefuroxime, a second generation Cephalosporin and moderately sensitive to Cephalexin (first generation) which may be used in pediatric cases as well. • Conclusions • The study indicates that antibiotics are prescribed on an empiric basis without any rationale. • Routine culture sensitivity testing is not being carried out in the hospital. • Culture Sensitivity testing is therefore a necessity for the rational use of antibiotics in the treatment of ASOM. • Based on the findings, Guidelines have been prepared and submitted to the ENT Department of Victoria Hospital in order to promote rational use of antibiotics.

13. Guidelines • First Line of Treatment • Symptomatic treatment with Amoxicillin till the results of the culture sensitivity tests are obtained. Recommended Dose and Duration: For pediatrics – 125 mg t.i.d to 750 mg b.i.d for 3 – 10 days. For adults – 250 – 500 mg every 8 hours for 10 days. • In case of beta lactam allergy • Co-trimoxazole: Recommended Dose and Duration: For pediatrics -TMP 8 mg , 40mg of SMZ/Kg body weight/day, in 2 divided doses for 10 days. For adults - One DS tablet (160 mg TMP and 800 mg SMZ) b.i.d for 10 days. • Or • Roxithromycin: Recommended Dose and Duration: For pediatrics – 2.5 – 5 mg b.i.d for 5-6 days. For adults - 150 mg b.i.d for 5-10 days. All dosage to be taken before meals. • Second Line of Treatment • In case of treatment failure with Amoxicillin, Amoxicillin/clavulanate can be used. Recommended Dose and Duration: For pediatrics - 40 mg/kg/day PO in divided doses every 8 hours or 45 mg/kg/day in divided doses every 12 hours for 10 days. For adults : 250 mg t.i.d for 10 days or 500 mg b.i.d for 10 days. • OR • Cefuroxime: Recommended Dose and Duration: For pediatrics: 40 mg/kg/day PO in divided doses b.i.d for 10 days. For adults: 250 mg – 500 mg b.i.d for 10 days. • In case of beta lactam allergy • Azithromycin: Recommended Dose and Duration: For pediatrics - 10mg/kg PO on day 1 followed by 5mg/kg daily from 2nd to 5th day. For adults : 500 mg OD for 5 days. • OR • Otic Ofloxacin or Ciprofloxacin 10 drops b.i.d for 14 days.

14. Third Line of Treatment • Cefotaxime: Recommended Dose and Duration: For pediatrics - Less than 50 kg, 50-180 mg/kg IM or IV in 4-6 divided doses. For adults - 1-2 gms t.i.d IM or IV. • Ceftriaxone: Recommended Dose and Duration: For pediatrics - 50-75 mg/kg/day IM OD for 3 days. For Adults - 1-2 gms IM or IV b.i.d for 4 -14 days. s The authors wish to acknowledge ‘WHO, South – East Asia Regional Office (SEARO)’, World Health House, New-Delhi, INDIA and ‘Al-Ameen College of Pharmacy’, Bangalore.