A comparative clinical study of sisomicin cream versus mupirocin ointment in pyodermas

Introduction

Topical anti-infective therapy is commonly employed for the treatment of pyodermas, which are caused predominantly by gram positive cocci. Sisomicin, a member of the aminoglycoside group of antibiotics, with established efficacy and safety[1] enjoys wide usage in India, while mupirocin is a newer topical antibiotic, effective primarily against gram positive cocci.[2] A review of the literature did not reveal any study comparing these two agents. The present study was therefore aimed at comparing their safety and efficacy in pyodermas.

Subjects and Methods

This was a prospective, randomised, parallel-group multicetric study that enlisted patients presenting with pyodermas requiring topical antibiotic therapy alone. The exclusion criteria were hypersensitivity to either sisomicin or mupirocin; any significant medical condition that in the judgement of the investigator might interfere with the study conduct; pregnancy and lactation. Eligible patients were assigned to treatment with either sisomicin or mupirocin based on a predesigned randomization schedule. Treatment with topical sisomicin cream (0.1%) twice a day, or mupirocin ointment (2%) thrice a day was given for a minimum of 7 and up to a maximum of 14 days. It was continued for at least 48 hours after the patients became asymptomatic. Therapy was terminated in cases of serious adverse effects, failure to respond to therapy or to comply with protocol requirements, or development of an intercurrent condition, which required discontinuation of the study medication and/or additional treatment. Patients were not allowed to take any other antibiotic (systemic or local) during the study.

At the time of enrollment, a written informed consent and a complete medical history was obtained and a thorough physical examination carried out. Six clinical parameters, viz. erythema, oedema, vesiculation, pustulation, cursting and scaling were evaluated using a 4-point grading system (0=none; not noticed by the physician or patient; 1=mild; noticed by the physician and/or patient, but not disturbing to the patient; 2=moderate; parameter definitely present and disturbing to the patient and interferes with some activity and/or sleep; 3 =severe; parameter very marked and very disturbing, interfering with most activities and/or sleep). Evaluation was done at baseline and days 4, 8 and 14. Efficacy of therapy was evaluated on the basis of reduction in the mean symptom scores at each follow up visit.

A pretreatment bacteriological examination of the lesion was performed to identify the causative pathogen and its sensitivity pattern in vitro. After completion of therapy, if a culture source was available, a post-treatment bacteriological evaluation was also done. The overall bacteriological response to therapy was classified as follows: elimination=causative organism absent at or immediately after termination of therapy, or the complete disappearance of the culture source so that follow-up culture is not possible; persistence=continued presence of causative organism at the end of treatment; reinfection =isolation of a new pathogen in any culture obtained in post-treatment period.

At the end of the study period for each individual patient, the investigator evaluated the response to therapy as follows: clear / marked improvement / moderate improvement / slight improvement / no change. The patient′s evaluation of the formulation was recorded as excellent/good/ fair. Adverse experiences, if any, were recorded with the date and time of onset, duration and severity (mild, moderate, severe) and the relationship to the study drug (unrelated, possible, probable and definite).

Statistical Analysis

Data was analysed at the end of the trial process. Demographic variables such as age, weight and sex were summarized. Bacterial elimination rate and clinical cure rate was compared statistically, using chi-squared (R2) test. The data measured on a continuous scale was compared using Students test. AP value v< 0.05 was considered significant.

Results

290 patients i.e. 147 on the sisomicin arm and 143 on the mupirocin arm, completed protocol-defined treatment and follow-up. There was no statistically significant difference between the two groups with regard to the number of patients, age and sex distribution or duration of infection. A pre-treatment bacteriological evaluation was possible in 132 patients on the sisomicin arm and 129 patients in the mupirocin arm. Both the groups were matched in the distribution of clinical conditions with impetigo being the commonest condition followed by folliculitis [Table - 1].

There was a progressive decline in the scores of erythema in both the groups, but the improvement was significantly more marked in the sisomicin group than that in the mupirocin group on days 4,8 and 14 [Figure - 1]. Sisomicin treatment also produced a greater improvement in the oedema scores than mupirocin, the difference being statistically significant on days 4 and 8 [Figure - 2].

The scores of vesiculation, pustulation and crusting all showed a steady improvement with treatment in both the groups, but the improvement with sisomicin was uniformly more marked than that with mupirocin; this difference was statistically significant at one or more time point [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6].

The reduction in the total mean score (for all evaluable clinical parameters) in the sisomicin arm vis-a-vis the reduction in the mupirocin arm was statistically significant on all days of followup. i.e. the improvement obtained with sisomicin treatment was statistically significant at all time points of follow up [Figure - 7].

The number of lesions showing complete clearance as evaluated by the attending doctor improved steadily with time in both the groups, with sisomicin leading to a more marked rate of clearance than mupirocin [Figure - 8].

Patients′ subjective evaluation which then used indicated a strong preference for sisomicin cream: 75% of the patients in the sisomicin arm rated the formulation as "excellent" compared to only 59% of the patients in the mupirocin arm (p< 0.001).

Staphylococcus aureus was isolated in whom a pre-treatment culture was positive (n=132 in sisomicin group and n=129 in mupirocin group). In addition to S. aureus, Streptococcus pyogenes was cultured in 39 patients in the sisomicin group and 34 patients in the mupirocin group. The bacteriological elimination rate was 97% with sisomicin therapy as against 94% with mupirocin.

No side effects were reported in either group.

Discussion

Pyodermas are common in India and are caused largely by Staphylococcus aureus and occasionally group a Beta-hemolytic streptococci. Topical therapy is generally the preferred mode of administering antibiotics in their management for reasons of convenience and ease of application.[3],[4] Systemic therapy may be necessary only if the lesions are generalised, if the regional lymph nodes are involved, if there is fever and/or if the lesions are deep as in the case of erysipelas, deep folliculitis, cellulitis and carbuncles.[5]

In order to be effective topically, an antibiotic must possess a broad antibacterial spectrum of action, good penetration to the site of infection, good tissue tolerance and effective resolution of clinical signs and symptoms. Sisomicin′s in vitro efficacy against a wide range of gram-positive and gram-negative clinical isolates, including gentamicin-resistant Pseudomonas aeruginosa, has been well established.[6] Its efficacy has also been documented in the management of superficial infections of skin and skin structures in Indian conditions.[7] Mupirocin is a newer topical antibiotic with food activity against gram-positive pathogens that is indicated for the treatment of infective dermatoses like imperigo.[8],[9] However the development of resistance to this agent is posing a challenge to infection control and antibiotic prescribing practice throughout the world.[10]

The present randomized study confirms the efficacy and safety of sisomicin and mupirocin in patients presenting with a variety of primary and secondary pyodermas. An important finding of this study was the greater and faster improvement of all evaluated clinical parameters with sisomicin as compared to mupirocin, which was statistically significant on all days of follow-up. This was reflected in the fact that a greater number of lesions in patients treated with sisomicin showed complete clearing on all days of follow-up. Also, a significantly greater number of patients rated sisomicin cream as an excellent formulation compared to mupirocin ointment.

Based on the findings of the present study, it may be concluded that sisomicin and mupirocin are safe and effective antibiotics in the management of pyodermas and that sisomicin offers advantages over mupirocin in terms of the faster and greater relief of various signs and symptoms.