Possible adverse events of imidazole antifungal drugs during treatment of vulvovaginal candidiasis: analysis of the FDA Adverse Event Reporting System.

Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.

Efficacy and safety of 250 mg versus 500 mg oral terbinafine in the treatment of tinea corporis and cruris: A randomised, assessor-blinded comparative study.

Background Though higher doses of terbinafine are often prescribed to treat dermatophyte infections, it is unknown if such doses are more effective than the conventional dose because comparative data are unavailable. Aim To compare the efficacy and safety of a once-daily dose of oral terbinafine 250 mg with 500 mg along with topical clotrimazole in the treatment of tinea infections. Methods A randomised, assessor-blinded, comparative study was carried out. Each group of subjects were administered either 250 mg or 500 mg oral terbinafine once daily for four weeks, along with topical clotrimazole. Clinical improvement was assessed after two weeks and again after four weeks from treatment initiation. Result A total of 60 patients with tinea corporis and cruris were randomised into two groups receiving either 250 mg (group A) or 500 mg (group B) oral terbinafine, along with clotrimazole cream in both groups. Baseline clinical parameters such as lesional activity (papules, vesicles and pustules), degree of erythema, scaling and severity of itching were comparable between both treatment arms. At the first and second follow-ups, no significant differences were found in the clinical parameters between the two groups. At the end of two weeks 13.8% of group A and 14.3% of group B and after 4 weeks 25.9% of group A and 33.3% of group B participants became KOH negative (P = 1.00 and 0.76, respectively). No significant difference in culture negativity was reported at the end of therapy (four weeks) between the two treatment arms (P = 0.78). Overall cure rates were 20% and 33.3% in the two treatment arms respectively at the end of the study (P = 0.82). Conclusion Oral terbinafine 250 mg daily yielded a poor cure rate in tinea cruris and corporis after 4 weeks of treatment and an increased dose of 500 mg did not have any additional benefit.

Topical azole treatments for otomycosis.

BACKGROUND: Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. OBJECTIVES: To evaluate the benefits and harms of topical azole treatments for otomycosis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). AUTHORS' CONCLUSIONS: We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.

Topical clotrimazole cream for the treatment of tinea cruris: A retrospective study.

This retrospective study assessed the efficacy and safety of 1% topical clotrimazole cream for the treatment of patients with tinea cruris (TC).We included 86 patients with confirmed TC for the presence of fungal hyphae. Of those, 43 patients received 1% topical clotrimazole cream for a total of 4 consecutive weeks, and were assigned to an experimental group. The other 43 patients underwent 1% topical butenafine cream for a total of 2 consecutive weeks, and were allocated to a control group. The efficacy and safety were measured and analyzed after 4 weeks treatment.After treatment, patients in both groups achieved better improvements in erythema (P < .01), scaling (P < .01), itching (P < .01), and KOH-negative results (P < .01), compared with those in patients before the treatment. However, there were not significant differences in erythema (P = .61), scaling (P = .57), itching (P = .47), and KOH-negative results (P = .67) between 2 groups. In addition, no treatment-related adverse events were recorded in both groups.Both 1% topical clotrimazole and butenafine cream are found to be effective and safe for patients with TC. However, there is not significant difference in efficacy and safety between two groups.

Impact of Process Parameters on Particle Size Involved in Media Milling Technique Used for Preparing Clotrimazole Nanocrystals for the Management of Cutaneous Candidiasis.

Clotrimazole is widely used for the management of cutaneous candidiasis infection. The low solubility of clotrimazole and excipient-related topical side effects (of currently available marketed products) cause the compromised efficacy of the therapy with poor patient compliance. In the present investigation, a clotrimazole nanocrystal-based nanogel was developed. Clotrimazole nanocrystals were optimized with studying the impact of individual process parameters of the media milling technique. The optimum level of individual process parameters was considered in the development of optimized batches. A promising result was obtained with a non-ionic stabilizer, polysorbate 80, at a concentration of 1.5%w/v, showing a distinct reduction in the particle size from above 31 µm to 264 nm and a polydispersity index of 0.211 with media milling at 1500 rpm for 6 h. This result was found to be in concordance with the TEM images, revealing a sharp diminution in particle morphology. Powder X-ray diffraction and differential scanning calorimetry results revealed crystallinity of clotrimazole (CTZ) in nanocrystal form. The optimized nanocrystal suspension was formulated into nanogel with carbopol 934, having a viscosity of 86.43 ± 2.06 Pa s at 25°C, which enhanced the ease of application of CTZ nanocrystals topically. A diffusion study showed around 82% of CTZ is transported across the membrane with the flux of 110.07 µg cm-2 h-1. In vivo results of the nanogel revealed improvement in CTZ release with 52% CTZ retention in different strata of the skin. The developed nanogel showed a significant improvement in the eradication of fungal infection within 10 days of application over Candida albicans-induced Wistar rat model. In a nutshell, the CTZ nanocrystal-loaded nanogel could achieve the goal of retaining CTZ in skin layers providing a prolonged effect and was able to treat cutaneous candidiasis in a short span with improved compliance for the candidiasis patients.

Role of Clotrimazole in Prevention of Recurrent Otomycosis.

Otomycosis is one of the relatively common diseases in the world which is caused by different fungi especially saprophytes. Concerning the relapse of this disease in a number of individuals, the present study was performed to evaluate the inhibitory effect of clotrimazole drop in the relapse of otomycosis. Clinical samples were taken by an ENT specialist from patients suspicious of having otomycosis. A part of these samples were stained, and others were cultured. The diagnosis of otomycosis was made on the basis of the recognizable and characteristic appearance of fungal hyphae or mycelium and fruiting bodies and/or conidiophores under microscopic examination. Patients with suspected otomycosis are not at risk of recurrence after treatment with clotrimazole drops. Out of the 161 individuals in whom definite diagnosis of otomycosis was made, the most affected individuals were, in the age range of 40-49 years, women, urban citizens, and housewives. Pruritus and diminished hearing were the main complaints of the patients. Aspergillus niger and A. flavus as well as Candida albicans were the main causes of the disease. The relapse of disease was observed in only five patients (3.1%), where A. niger was the main fungus. Most relapses were observed in women and in those with diminished hearing, manipulating the ears, ulcers in the canal, and tympanum. Our results suggested that usage of clotrimazole can be effective in reducing the relapse of otomycosis, and concerning the high cost of treating otomycosis while the low cost of using clotrimazole, usage of this drop is recommended to reduce the relapse of otomycosis.

An Unusual Manifestation of Calcineurin Inhibitor-Induced Pain Syndrome in Kidney Transplantation: A Case Report and Literature Review.

BACKGROUND Calcineurin inhibitors (CNI) are the mainstay immunosuppressive drugs for kidney transplantation. Although they provide excellent allograft and patient outcomes, adverse effects are frequently encountered. Calcineurin inhibitor-induced pain syndrome (CIPS) is a rare adverse effect of CNI. Previous case reports with CIPS diagnosis involved incapacitating pain in the lower extremities. CASE REPORT In this article, we report the first case of CIPS with severe back pain as the presenting symptom, which was correlated with a high tacrolimus trough concentration due to a drug interaction with clotrimazole troche. Magnetic resonance imaging (MRI) of the spine showed bone marrow edema, which is consistent with previous case reports. The patient's symptoms resolved within 3 weeks of the onset of pain. Treatments were symptomatic care and lowering the tacrolimus trough concentration. Pain was improved significantly with pregabalin but not with nifedipine. CONCLUSIONS We reviewed the literature of kidney transplant cohorts with CIPS to ascertain prevalence, pain characteristics, and treatment outcomes. Apart from our case, all patients experienced lower extremities pain and were pain-free during the follow-up period, without any residual abnormalities. CIPS is a benign but adverse effect of CNI. Counselling patients about the disease's natural history and supportive care remain the best treatment.

Clotrimazole is effective for the regression of endometriotic implants in a Wistar rat experimental model of endometriosis.

The present work aimed to evaluate molecular, angiogenic and inflammatory changes induced by clotrimazole (CTZ) on endometriosis lesions. For this, thirty female Wistar rats with surgically implanted autologous endometrium were treated with CTZ or vehicle (200 mg/kg) via esophageal gavage for 15 consecutive days. CTZ treatment significantly decreased the growth and the size of the implants, and histological examination indicated regression and atrophy, with no toxicity to the animals. The levels of the angiogenic markers VEGF and VEGFR-2 were significantly decreased in CTZ group. The treatment also promotes a reduction on PGE2 and TNF-α levels. All these effects involve the amelioration of ERK1/2, Akt, AMPK and PERK signaling upon CTZ treatment. In conclusion, CTZ promoted an overall amelioration of endometriosis in a rat model due to the anti-angiogenic properties of the drug. Therefore, our results support the proposal of a clinical trial using CTZ for the treatment of endometriosis.

Acute vanishing bile duct syndrome after therapy with cephalosporin, metronidazole, and clotrimazole: A case report.

RATIONALE: Vanishing bile duct syndrome (VBDS) consists of a series of diseases characterized by the loss of >50% bile duct in portal areas. Many factors are associated with VBDS including infections, neoplasms, and drugs. Antibiotic is one of the most frequently reported causes of VBDS. PATIENT CONCERNS: A 29-year-old female was admitted because of liver injury for over 3 months. Tests for viruses that can cause hepatitis and autoantibodies were all negative. She was prescribed with antibiotics approximately a week before liver injury while there was no history of alcohol consumption. DIAGNOSES: Liver biopsy demonstrated a loss of intrahepatic bile duct in most of the portal tracts. INTERVENTIONS: This patient was treated with ursodeoxycholic acid, polyene phosphatidylcholine, and bicyclol. Most importantly, the treatments in our hospital were proved by the ethics committee of Department of Infectious Disease, Anhui Provincial Hospital. OUTCOMES: The symptoms were improved. She is still under treatment. LESSONS: VBDS is rare but can be severe. A liver biopsy offers an important evidence for the diagnosis of VBDS, especially for those with a history of susceptible drugs taking.

The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme.

Cryptococcosis is a life-threatening disease often associated with HIV infection. Three Cryptococcus species CYP51 enzymes were purified and catalyzed the 14α-demethylation of lanosterol, eburicol, and obtusifoliol. The investigational agent VT-1129 bound tightly to all three CYP51 proteins (dissociation constant [Kd] range, 14 to 25 nM) with affinities similar to those of fluconazole, voriconazole, itraconazole, clotrimazole, and ketoconazole (Kd range, 4 to 52 nM), whereas VT-1129 bound weakly to human CYP51 (Kd, 4.53 µM). VT-1129 was as effective as conventional triazole antifungal drugs at inhibiting cryptococcal CYP51 activity (50% inhibitory concentration [IC50] range, 0.14 to 0.20 µM), while it only weakly inhibited human CYP51 activity (IC50, ∼600 µM). Furthermore, VT-1129 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. Finally, the cellular mode of action for VT-1129 was confirmed to be CYP51 inhibition, resulting in the depletion of ergosterol and ergosta-7-enol and the accumulation of eburicol, obtusifolione, and lanosterol/obtusifoliol in the cell membranes.

The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder.

Clinically Significant Drug Interaction Between Clotrimazole and Tacrolimus in Pancreas Transplant Recipients and Associated Risk of Allograft Rejection.

STUDY OBJECTIVE: To examine the clinical significance of clotrimazole troche discontinuation on tacrolimus trough levels and risk of allograft rejection after pancreas transplantation. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Sixty-five pancreas transplant recipients (simultaneous pancreas-kidney transplants [39 patients], pancreas after kidney transplants [4 patients], and pancreas transplant alone [22 patients]) who were discharged after transplantation receiving a maintenance immunosuppressive regimen of tacrolimus, mycophenolate, and prednisone, and a clotrimazole troche to prevent oral mucosal candidiasis; per protocol, the clotrimazole troche was discontinued at 3 months after transplantation. MEASUREMENTS AND MAIN RESULTS: Patients were followed for 1 year after transplantation. The primary outcome measure was the difference in tacrolimus trough level before and after discontinuation of the clotrimazole troche. The secondary outcome measure was the difference in tacrolimus trough level when patients were stratified by the cohort that had a documented rejection episode 3-12 months after transplantation (rejection group) and the cohort that did not experience a rejection episode (no-rejection group). The incidence of rejection was evaluated in relation to mean tacrolimus trough concentrations above or below a protocol-defined level of significance (6 ng/ml). For the primary outcome, the mean tacrolimus trough level before discontinuation of the clotrimazole troche was significantly higher than the mean trough level after discontinuation (mean ± SD 9.6 ± 3.0 ng/ml vs 7.1 ± 2.6 ng/ml, p = 0.000003). For the secondary outcome, the mean tacrolimus trough level difference before and after clotrimazole troche discontinuation remained significant in both the no-rejection group (9.5 ± 3.0 ng/ml vs 7.4 ± 2.4 ng/ml, p = 0.00007) and rejection group (10.9 ± 3.3 ng/ml vs 4.1 ± 2.5 ng/ml, p = 0.0008). Between groups, the mean tacrolimus serum trough level after clotrimazole troche discontinuation was lower in the rejection group (4.1 ± 2.5 ng/ml) than that in the no-rejection group (7.4 ± 2.4 ng/ml; p = 0.005). The mean tacrolimus trough level difference between before and after discontinuation was greater in the rejection group (6.8 ± 1.5 ng/ml) versus the no-rejection group (2.1 ± 3.8 ng/ml, p = 0.009). Tacrolimus trough levels below 6 ng/ml (19 patients) after clotrimazole troche discontinuation were associated with an increased incidence of rejection episodes within 3-12 months after transplantation (odds ratio 12, 95% confidence interval 1.24-115.91, p = 0.032) versus trough levels of 6 ng/ml or higher (46 patients). CONCLUSION: Clotrimazole troche discontinuation at 3 months after transplantation may cause significant tacrolimus trough level reductions. In addition, when trough levels are below 6 ng/ml, these fluctuations may contribute to the occurrence of allograft rejection.

Clotrimazole troches induce supratherapeutic blood levels of sirolimus and tacrolimus in an allogeneic hematopoietic cell-transplant recipient resulting in acute kidney injury.

Allogeneic hematopoietic cell transplantation is a potential curative treatment option for various malignant and nonmalignant hematologic disorders. Patients undergoing an allogeneic hematopoietic cell transplant are prescribed immune-suppressant therapies to facilitate hematopoietic donor-cell engraftment and prevent graft-versus-host disease. Drug-drug interactions may occur, owing to exposure to complex multidrug regimens with narrow therapeutic windows and high toxicity profiles. Here, we describe a unique case of a 65-year-old man with poor-risk acute myeloid leukemia who underwent a matched-sibling hematopoietic cell allograft. Sirolimus and tacrolimus were used for graft-versus-host disease prophylaxis. He developed oral thrush requiring treatment with clotrimazole troches, which subsequently resulted in serious renal toxicity attributed to supratherapeutic levels of sirolimus and tacrolimus. Patient renal function improved after temporarily holding both immune suppressants, and administering phenytoin to help induce sirolimus and tacrolimus metabolism. This case highlights sudden and serious toxicities that resulted from clotrimazole-sirolimus and clotrimazole-tacrolimus drug-drug interactions, even when administered topically.

Clotrimazole as a pharmaceutical: past, present and future.

Clotrimazole is a broad-spectrum antimycotic drug mainly used for the treatment of Candida albicans and other fungal infections. A synthetic, azole antimycotic, clotrimazole is widely used as a topical treatment for tinea pedis (athlete's foot), as well as vulvovaginal and oropharyngeal candidiasis. It displays fungistatic antimycotic activity by targeting the biosynthesis of ergosterol, thereby inhibiting fungal growth. As well as its antimycotic activity, clotrimazole has become a drug of interest against several other diseases such as sickle cell disease, malaria and some cancers. It has also been combined with other molecules, such as the metals, to produce clotrimazole complexes that show improved pharmacological efficacy. Moreover, several new, modified-release pharmaceutical formulations are also undergoing development. Clotrimazole is a very well-tolerated product with few side effects, although there is some drug resistance appearing among immunocompromised patients. Here, we review the pharmaceutical chemistry, application and pharmacology of clotrimazole and discuss future prospects for its further development as a chemotherapeutic agent.

[Investigation of antibacterial activity of topical antimicrobials against methicillin-resistant Staphylococcus aureus].

OBJECTIVE: To investigate the antibacterial activity of silver sulfadiazine (SD-Ag), mupirocin, and clotrimazole used alone or in combination against methicillin-resistant Staphylococcus aureus (MRSA) isolated from burn wounds. METHODS: Eighteen MRSA isolates from wound excretion of 18 burn patients hospitalized in our unit from July to December 2011 were collected continuously and non-repetitively. (1) Minimum inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of SD-Ag, mupirocin, and clotrimazole used alone, those of SD-Ag and mupirocin used in combination, and those of SD-Ag, mupirocin, and clotrimazole used in combination to MRSA were determined by checkerboard agar dilution method. (2) Fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of SD-Ag plus mupirocin, and SD-Ag plus mupirocin and clotrimazole. Synergy with FIC index less than or equal to 0.5 or additivity with FIC index more than 0.5 and less than or equal to 1.0 was regarded as effective, and indifference with FIC index more than 1.0 and less than or equal to 4.0 or antagonism with FIC index more than 4.0 was regarded as ineffective. The effective ratio was compared with overall ratio (assumed as 0) by unilateral binomial distribution test. RESULTS: The MIC, MIC50, and MIC90 of SD-Ag, mupirocin, and clotrimazole used alone against 18 MRSA isolates were respectively 8, 8, 16 µg/mL; 2, 16, 64 µg/mL; 2, 2, 2 µg/mL. MIC of antimicrobial agents used in combination decreased from 3.1% to 50.0% as compared with that of individual agent used alone. Compared with those of single application of SD-Ag and mupirocin, MIC50 of SD-Ag and that of mupirocin both decreased 75.0%, and MIC90 of them decreased 87.5% when SD-Ag and mupirocin were used in combination. Compared with those of single application of SD-Ag, mupirocin, and clotrimazole, MIC50 of SD-Ag, mupirocin, and clotrimazole respectively decreased 75.0%, 87.5%, and 50.0%; MIC90 of them respectively decreased 87.5%, 96.9%, and 50.0% when SD-Ag, mupirocin, and clotrimazole were used in combination. Among the 18 MRSA isolates, the combined effect of SD-Ag and mupirocin was synergic in 9 isolates, additive in 7 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate; the combined effect of SD-Ag, mupirocin, and clotrimazole was additive in 16 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate. There were statistically significant differences between effective ratio and overall ratio of 18 MRSA isolates treated with combined antimicrobial agents (P values all above 0.01). CONCLUSIONS: For burn wounds at middle and late stages infected with Staphylococcus aureus or Staphylococcus aureus and Fungus, low dose of SD-Ag or combination of above-mentioned antimicrobial agents can effectively control infection and decrease the adverse effect of antimicrobial agents on wound healing.

The use of extemporaneously compounded 1% tetracaine to improve adherence with clotrimazole 1% topical solution in the treatment of ear infection: a case report.

For most medically amenable conditions, adherence to drug therapy is a necessary condition for a successful outcome. Drug side effects, especially pain, can interfere with the desired outcome. We report a case of non-adherence due to severe pain associated with the topical use of clotrimazole 1% solution in the ear. Instillation of tetracaine 1% solution prior to the administration of the clotrimazole blocked the pain sensation allowing the patient to successfully complete the antifungal therapy.