JOURNAL READING

Comparative Efficacy and Safety of Various Anti-Microbials in Patients of Acute Rhinosinusitis at Tertiary-Care

Hospital in Uttarakhand (UK)Vivek Sharma, R. K. Saxena, Geetanjali Sharma, K. C. Mishra, Shalini Sharma,

D. C. Dhasmana Association of Otolaryngologists of India 2011

Created By :Nyoman Aditya Sindunata (FK

UPH)Fitria Ayu Anggraini (FK UPN)

Pembimbing :dr. Khairan, Sp.THT K-L

Abstract

To compare the efficacy of gatifloxacin, azithromycin with amoxicillin as positive control for the treatment of Acute rhinosinusitis (ARS).

To monitor adverse drug reaction profile of amoxicillin, azithromycin and gatifloxacin in

patient of ARS.

An open randomized trial of comparative efficacy and safety of amoxicillin,

azithromycin and gatifloxacin in patients with ARS

Introduction

Rhinosinusitis is a global problem

It is usually a disease of sino-nasal obstruction and bacterial trapping. It is usually preceded by and

occurs in tandom with viral URTI.

Sinusitis is considered to be inherent part of the ‘‘common-cold syndrome’’ and hence the term

rhino-sinusitis defines this disease more precisely.

When the sinus ostium is obstructed, the retained secretions may become infected with a variety of pathogens, including viruses, bacteria and fungi

There is always a preceding viral upper respiratory infection which gets superimposed by bacterial

infections.

for which antibiotics are commonly prescribed in 85–95% of cases.

Inspite of disease being very common, there is likely possibility of it being often mis-diagnosed. At the same time disease warrants early diagnoses and

timely antimicrobial treatment so as to avoid complications.

The treatment of such a condition is still emprical and quite controversial in terms of anti-bacterial drug of choice,

frequency, route and duration of treatment and other adjuvant drugs

being used.

There is no general consensus among physicians world-wide with regard to drug treatment of this disease. So the present study was envisaged to

compare different anti-microbial drugs in treatment of ARS.

Materials and Methods

STUDY DESIGN

An open randomized trial of comparative efficacy and safety of amoxicillin, azithromycin and gatifloxacin in patients with Acute rhinosinusitis (ARS).

SUBJECTS

Adults patients presenting in ENT OPD at HIMS, Jolly Grant, Dehradun during the course of 1 year with a primary diagnosis of clinically and radiologically documented acute sinusitis of less then or equal to 4 weeks duration were enrolled with us.

Eligible adults of either sex of at least 18 years of age were enrolled.

Use of adjunctive treatment such as antipyretic, phenylephrine nose drops or xylometazoline spray were allowed.

With symptoms lasting for more than 1 week or those with severe rhinosinusitis symptoms : Nasal discharge of any quality Facial pain unrelated to trauma Predominantly unilateral maxillary pain Maxillary toothache or pain when

chewing Unilateral pain above and below eyes on

bending forward.

INCLUSION CRITERIA

Patient with chronic symptoms ([1 month)

Immuno compromised patient

Patient with previous sinus surgery.

Patient with antibiotic use with in past 1 week.

Co-morbidity (diabetes, heart failure, immune deficiency).

Pregnancy/breast-feeding.

In take of antibiotics for less than 4 weeks.

Other nasal disorders (nasal polyps).

Concurrent bronchitis, current episodes of longer than 3 months.

Know hypersensitivity to pencillins, macrolides, fluoro-qunolones.

Hepatic, renal or immunological disorders.

Coagulation disorders.

Seizure disorder or any condition requiring therapy with major tranquilizers.

Patients who required nasal or systemic steroids.

EXCLUSION CRITERIA

Baseline Characteristics

Demographic characteristics Age, sex, occupation, socio-economic

status Relevant medical history -> ENT

examination

Diagnostic Criteriaat least 2 major / 1 major + 2 minor

Major Factors• Facial pain / pressure• Facial congestion / fullness• Nasal obstruction• Purulent rhinorrhoeae / discoloured

postnatal discharge• Hyposmia or anosmia• Fever with preceding URTI

Minor Factors• Headache• Halitosis (foul breath)• Fatigue• Dental pain (maxillary toothache)• Cough

Antimicrobial Therapy and Assessment

After meeting criteria -> 3 groups @ 10 patients : Group 1: Patients on oral amoxicillin 500 mg TDS for 10

days. Group 2: Patients on oral azithromycin 500 mg OD for

5 days. Group 3: Patients on oral gatifloxacin 400 mg OD for 10

days.

Evaluation of signs and symptoms : Day 1 Primary end point : day 7 (group 2), day 12 (group 1,

3) Secondary end point : 28 days after post therapy

Evaluation of Efficacy

Assessment of clinical signs and symptoms

Overall clinical response rating and radiographic findings

Water’s view before and after drug treatment (primary end point and secondary end point)

Radiographic Findings and Assessment

On admission and 2 days after the end of therapy

Assessment : resolved, improved, worsened, or unchanged

Evaluation of Safety

Done simultaneously : monitoring adverse drug reaction (each hospital visit)

Grade : Mild : sign and symptoms, easily

tolerated Moderate : discomfort -> affect daily

activity Severe : inability to work /

hospitalization / permanent disability / life-threatening

Statistical Analysis

Done to test the efficacy Applying student’s t-test Results – reported according to an

intent-to-treat analysis

Observation and Results

Intra-Group Comparisons Group I – amoxicillin (positive control)

Highly significant fall of scoring : day 12 (P<0.001) and 40 (P<0.001)

Group II – azithromycin Effective in significant reduction : day 7 (P<0.001) and 35

(P<0.01) Group III – gatifloxacin

Effective in significant reduction : day 12 (P<0.001) and 40 (P<0.001)

*significant reduction in symptoms of acute sinusitis on visual analogue scale

Inter-Group Comparisons

Effective : azithromycin = amoxicillin Reducing symptoms (VAS) on day 7 and

35 (P > 0.05) Most effective : gatifloxacin

Reducing symptoms (VAS) on day 12 (P < 0.02) and 35 (P < 0.05), compared to amoxicillin

Intra-Group Comparisons (radio.)

Group I – amoxicillin (positive control) Significant improvement : day 12 (P<0.05) and

40 (P<0.01) Group II – azithromycin

Significant improvement : day 12 (P<0.05) and 40 (P<0.001)

Group III – gatifloxacin Highly significant improvement : day 12

(P<0.001) and 40 (P<0.001)

*significant improvement in radiographic improvement

Inter-Group Comparisons (radio.)

Azithromycin : significant improvement (radiographic) on day 7 (P < 0.01) and 35 (P < 0.01)

Gatifloxacin : Very highly significant improvement

(radiographic) on day 40 (P < 0.001) Significant improvement on day 12 (P <

0.01), compared to amoxicillin

Discussion

Primary goals of management of acute sinusitis : Eradicate infection (systemic

antimicrobial treatment) Decrease the severity and duration of

symptoms Prevent complications, i.e. micocoele,

chronic sinusitis Amoxicillin, azithromycin and

gatifloxacin Effective : reducing symptoms on VAS

scoring

Summary and Conclusions

Amoxicillin, azithromycin, gatifloxacin Effective : reducing sign and symptoms – VAS

Gatifloxacin Most effective drug : sign and symptoms – VAS

and radiographic scoring Least adverse events (mild), compared to other

Azithromycin : 2nd safest drug (less adverse effects)

Conveniece of dosing -> patients compliance

Conclusion : gatifloxacin – drug of choice Further study : prevalent nature of disease

and smaller sample size

Terima Kasih