Management of acute bacterial sinusitis : a prospective observational , multicenter study focusing on the safety and efficacy of Moxifloxacin

1HOD &Consultant ENT, DHQ Rawalpindi, Pakistan 2Prof & Consultant ENT, Jinnah Hospital, Lahore, Pakistan 3Assistant Professor & Consultant ENT, Abbasi Shaheed Hospital, Karachi, Pakistan 4Professor Consultant ENT, Fatima Jinnah Medical University, Lahore, Pakistan 5Assoc Prof &Consultant ENT, Saifee hospital, Karachi, Pakistan 6Associate Professor &Consultant ENT, King Edward medical university, Pakistan 7Professor Consultant ENT Civil hospital, Karachi 8Professor, Consultant ENT, Ghurki Medical College, Gujranwala, Pakistan 9Manager Medical Affairs & Clinical Research, Hilton Pharma Pvt Ltd, Pakistan 10Sr. Director Medical, Regulatory & business development, Hilton Pharma Pvt ltd, Pakistan 11Sr. Lecturer, Al tibri medical college, Karachi, Pakistan International Journal of Open Access Otolaryngology Open Access Research Article


Introduction
A well predictable and common health problem is acute sinusitis which primarily affects the maxillary sinuses but its disease burden is often considered insignificant.The bacteria most often responsible for acute sinusitis include Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis.Otherbacterial pathogens, such as Staphylococcus aureus, Enterobacteriaceae and anaerobic bacteria are the rare causative agents [1].Sinus involvement is frequently associated with the common cold.Thus, the condition probably is well pronounced as viral rhino sinusitis (VRS) rather than sinusitis.An estimated 1 billion of such cases of VRS occur each year in the United States.However, around 0.5% to 2% of VRS cases in the United States are complicated by secondary bacterial infections of the sinuses [2].It was estimates that over 25% of the population suffer from rhinosinusitis with significant associated comorbidities which considerable effects on quality of life and educational performance [3].An acute viral or bacterial infection categorized by inflammation of the nose mucosa and paranasal sinuses is considered as Acute Rhinosinusitis (ARS) [4].An acute bacterial rhinosinusitis is equally communal in incidence; however most cases are of viral basis.There is a prompt improvement in most of patients without antibiotic therapy but it must be considered in patients with extended or more severe indications.Rhinosinusitis is considered to be acute (viral or non-viral origin) if it lasts less than 12 weeks, and chronic when it exceeds more than 12 weeks.However, if it occurs with three or more episodes in one year, then is considered as recurrent.In 40% of the cases its symptoms disappear spontaneously without and therapy.However, medical treatment is specified to reduce the symptoms, hasten the improvement of the clinical features and avoid apparent complications [5].The signs and symptoms of Acute Bacterial Sinusitis (ABS) include nasal obstruction or stuffiness, mucopurulent nasal expulsion or postna sal dribble, facial pain, headache, and decrease or loss of smell and observation of bad smell (cacosmia).Signs include erythematous nasal turbinate, mucopurulent nasal discharge of meatus and post nasal drip [6].
Antimicrobial agents and local nasal decongestant like corticosteroids used in combination or as a solitarytreatment have verified theraupatic utility in controlled experimental trials [7,8].
Accumulative resistance of organisms to regularlyemployed antibiotics presents a challenge in the treatment of sinusitis.However, Fluoroquinolones are not demolished by betalactamase-producing organisms and are therefore used as substitute treatment operative against gram-negative pathogens, such as H. influenzae and M. catarrhalis.Some quinolones also have activity against S. pneumoniae, including multidrug resistant strains Moxifloxacin is a new 8-methoxyfluoroquinolone antibacterial agent [9,10,11,12].Moxifloxacin has a extended half life with high capacity of dissemination.It is The Symptoms was compared at 3 rd and 7 th day of treatment.It was noticed that symptoms were absent in 113 (65.7%) respondents at 7 th day.Mild symptoms were decreased to 57 (33.1%) and sever symptoms were reduced to 2 (1.2%) .A significant difference was found with p value of 0.007 (Table 2, Figure 2) The comparison of symptoms at 3 rd and 14 th day period revealed that they were absent in 152 (88.4%) patients at 14 th day, while mild and severs symptoms were reduced to 17(9.9%) and 3(1.7%) patients with a significant p value of 0.004.(Details are given in Table 3, Figure 3) The symptoms were compared at 7 th and 14 th day period.It was noticed that symptoms were absent in 152 (88.4%) patients at 14 th day.Mild symptoms were decreased to 17 (9.9%)and sever symptoms were reduced to 3(1.7%) patients with a p-value of 0.000 (Table 4, Figure 4)

Management of acute bacterial sinusitis: a prospective observational, multicenter study focusing on the safety and efficacy of Moxifloxacin
Copyright: © 2017 Medical Dept Hilton Pharma Pvt Ltd.
well absorbed orally and recent studies have shown that it has predominantly good activity against S.pneumoniae, H. infuenzae and M. catarrhalis.These organisms are important causative agents of respiratory and sinus infections [13,14].The high concentration of moxifloxacin at the site of infection is due to its good tissue penetration, that becomes progressively significant with the range of antibiotic-resistant strains [15].
This study was intended to recognize the usefulness of moxifloxacin in patients with acute bacterial sinusitis in Pakistani population.The purpose ofthis study was to observe the efficacy, safety in terms of adverse events other than side effects & tolerability of moxifloxacin in patients with Acute Bacterial Sinusitis across Pakistan.

Materials and methods
This was the prospective, observational multicenter study in patients diagnosed with Acute Bacterial Sinusitis treated with Moxifloxacin therapy.The convenient sampling technique was used to select the patients.The ethical approval was taken by the institutional research forum of Rawalpindi Medical College.The study population comprised of approximately 200

Management of acute bacterial sinusitis: a prospective observational, multicenter study focusing on the safety and efficacy of Moxifloxacin
Copyright: © 2017 Medical Dept Hilton Pharma Pvt Ltd.
male and female patients with a diagnosis of acute bacterial sinusitis on clinical basis for whom fourth-generation synthetic fluoroquinolone antibacterial agent Moxifloxacin daily is recommended by the treating physician.The dose of Moxifloxacin is 400 mg once every 24 hours.Out of 200 patients 28 were excluded from the study due to incomplete proforma and lost to follow ups.
Patient data originating from assessments and estimations executed according to the physician's routine practice was composed.As per discretion of doctor Moxifloxacin therapy was prescribed to the newly diagnosed & known patients of Sinusitis.All patients were screened as per inclusion & exclusion criteria.The patients who were willing to participate, had give informed consent, were having the age of greater than 18 years with signs and symptoms of acute bacterial rhinosinusitis including nasal blockage or stuffiness, mucopurulent nasal discharge or postnasal drip, facial pain, headache, and reduction or loss of smell or perception of bad smell and has never been treated with the moxifloxacin were included in the study.The patients were diagnosed on clinical basis.The patients having known hypersensitivity to moxifloxacin previously were excluded from the study.
The observational period comprised of four 04 visits.An initial visit and third day follow-up visits was recognized, followed by a visit on seventh day and fourteenth day at the end of therapy.
Symptoms of Acute Bacterial Sinusitis (fever, cough, nasal obstruction, nasal secretion, facial pain with feeling of fullness and headache) were assessed at baseline and at follow-up visits, and classified as 'absent', 'mild' or 'severe' by the attending physician.
The course of symptoms during moxifloxacin therapy was analyzed in terms of the categories 'cured', 'improved', 'unchanged' or 'worse'.The patient's satisfaction with moxifloxacin therapy was assessed on a 4-point scale from 'insufficient' to very good.
All patients were treated with 400 mg/day of moxifloxacin orally for fourteen days in combination with anti-inflammatory and anti-allergic medicine.Patients were instructed to take each dose of moxifloxacin at the same time every day, while antiinflammatory and anti-allergic medicine was prescribes thrice and twice a day respectively.
The safety assessments consisted of observing and recording all adverse events AEs) and serious adverse events (SAEs).

Data analysis
Data analysis was done through the software SPSS version 20.0.For continuous variables, summary statistics included mean, standard deviation, median, minimum and maximum values, as well as frequencies and percentages for categorical variables are presented.Kendall's tau-b test and Chi square test was to see the significance at different levels of treatment at 3rd day, 7th day and 14th day period.P-values of< 0.05 are considered to be significant.

Results
A total of 172 patients were includedwithAcute Bacterial Sinusitis.Mean age of the patient was found to be 33.51±9.6 years.Male were found to be 108 (63%) while rest were female 64 (37 %).
The most common adverse effect was dizziness that was found in 30% of the cases followed by nausea and vomiting, others like palpitation, body ache and gastric upsets and dry mouth in 7%, 6% and 4% cases respectively.There was no report of the serious adverse events.

Discussion
The aim of antibiotic remedy is to eliminate bacterial pathogens at the site of infection.It has been established that the failure of antibiotic to achieve this goal increases the potential for clinical failure, adds further costs, and may be due to selection of antibiotic with bacteria were resistant [16].
The common symptom was nasal discharge (98.3%) followed by nasal obstruction or stuffiness, postnasal drip, headache, facial pain, reduced smell and cacosmia [17].This is inconsistent with our study in which headache (95%) and fever (91%) are the commonest symptoms followed by cheek tenderness (88%) and purulent discharge in 85% of cases.
There was no phototoxicity in patients treated with moxifloxacin as it is believed that the methoxy group at the 8-position on moxifloxacin confers decreased photo toxicity which is in accordance to our study which did not reveal any of the phototoxic effect of moxifloxacin.
In one of the study the most common adverse events reported were vomiting (4.35%) and nausea (4.35%).Whereas in our study vomiting was found in 7% of the cases and dizziness was the most common side effect found in 30% of patients.Dizziness and headache are the common clinical presentation of acute bacterial sinusitis hence further studies are needed to identify the relationship of this side effect with moxifloxacin.
It was suggested by a worldwide assessment of response to treatment with moxifloxacin that the electrocardiogram records after treatment did not show any evidence of increate QT intervals which reflects the complete valuation on the collective parameters of efficacy and safety that is consistent with our study in which clinically no cardiac toxicity is reported.
In one of the study physician's overall assessment showed that 91.31% of patients treated with moxifloxacin group had excellent-to-good response to treatment which is balanced with our study in which 85 % of the patients were completely cured and 10 % were improved [18].There was no occurrence of any serious adverseconsequence during the study.
The assistances of this study are that our suitable collection methodology has qualified that we have sampled the accounts of extensive range of physician and patients perspectives and their proficiencies of treating the patients of acute bacterial sinusitis.Furthermore, it delivers wide extractions of the practitioner's perceptions.However, there are some detriments found in this study such as observer and recall bias.Reflecting the opinions of patients and experience and to what range they are reliable with those of the general physicians would be enlightening and valuable to standardize the misapprehensions about the treatment of the disease.

Conclusion
Moxifloxacin is effective in resolving the symptoms of acute bacterial sinusitis.It is more effective than other antibiotics because of its efficacy and least side effects.The medicating of simple once daily dosage offer benefits over many existing agents in terms of compliance as well.

Table 1 :
Clinical features of Acute Bacterial Sinusitis

Table 2 :
Symptoms of ABS on 3rd Day and 7th day

Table 3 :
Symptoms of ABS 3rd Day vs 14th day *Kendall's tau-b test applied to see the significance

Table 4 :
Symptoms of ABS 7th Day vs 14th day

Variable 7 th Day 14 th Day Frequency Percent Frequency Percent P-Value
*Kendall's tau-b test applied to see the significance

Table 5 : Patient Condition 3rd day vs 7th day
Chi square test applied to see the significance It was noticed that on 7 th day as compared to the 3 rd day the patients were cured and improved in 96 (55.8%) and 66 (38.4%) respectively with a significant p value of 0.047.(Table5)

Table 6 : Patient Condition 3rd day vs 14th day Frequency Percent Frequency Percent P-value
Chi square test applied to see the significance It was noticed that on 14 th day as compared to the 3 rd day the patients were cured and improved in 146 (84.9%) and 17 (9.9%)respectively with a significant p value of 0.034.(