ABSTRACT
Fusidic acid (FA) had excellent antimicrobial effects due to its unique mechanism of action. Since 1962, FA has been widely used in the systemic and topical treatment of staphylococcal infections and exhibits a well-characterized potency against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative Staphylococci. In view of the spectrum of activity, no cross-resistance with other clinically used antibiotics, and potential penetration into brain tissue, FA was used to treat possible gra-positive bacteria in 3 patients with intracranial infections in the present report. FA and its active metabolite (3-keto FA) were measured in plasma and cerebrospinal fluid (CSF) to assess the treatment of FA, and the results indicated that 1,500 mg per day of FA was sufficient to achieve therapeutic concentrations in both plasma and CSF in intracranial infection patients, while the dosage did not experience unexpected regimen-related toxicity.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Fusidic Acid/therapeutic use , Fusidic Acid/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus , Microbial Sensitivity TestsABSTRACT
BACKGROUND: Impetigo, a highly contagious bacterial skin infection commonly occurring in young children, but adults may also be affected. The superficial skin infection is mainly caused by Staphylococcus aureus (S. aureus) and less frequently by Streptococcus pyogenes (S. pyogenes). Antimicrobial resistance has become a worldwide concern and needs to be addressed when selecting treatment for impetigo patients. An evidence-based impetigo treatment algorithm was developed to address the treatment of impetigo for pediatric and adult populations. METHODS: An international panel of pediatric dermatologists, dermatologists, pediatricians, and pediatric infectious disease specialists employed a modified Delphi technique to develop the impetigo treatment algorithm. Treatment recommendations were evidence-based, taking into account antimicrobial stewardship and the increasing resistance to oral and topical antibiotics. RESULTS: The algorithm includes education and prevention of impetigo, diagnosis and classification, treatment measures, and follow-up and distinguishes between localized and widespread or epidemic outbreaks of impetigo. The panel adopted the definition of localized impetigo of fewer than ten lesions and smaller than 36 cm2 area affected in patients of two months and up with no compromised immune status. Resistance to oral and topical antibiotics prescribed for the treatment of impetigo such as mupirocin, retapamulin, fusidic acid, have been widely reported. CONCLUSIONS: When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Critical Pathways/standards , Impetigo/drug therapy , Staphylococcus aureus/drug effects , Streptococcus pyogenes/drug effects , Aminopyridines/pharmacology , Aminopyridines/therapeutic use , Anti-Bacterial Agents/pharmacology , Antimicrobial Stewardship/standards , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Delphi Technique , Diterpenes/pharmacology , Diterpenes/therapeutic use , Drug Resistance, Bacterial , Evidence-Based Medicine/standards , Fusidic Acid/pharmacology , Fusidic Acid/therapeutic use , Humans , Impetigo/diagnosis , Impetigo/microbiology , Microbial Sensitivity Tests/standards , Mupirocin/pharmacology , Mupirocin/therapeutic use , Practice Guidelines as Topic , Quinolones/pharmacology , Quinolones/therapeutic use , Skin Cream/pharmacology , Skin Cream/therapeutic use , Staphylococcus aureus/isolation & purification , Streptococcus pyogenes/isolation & purification , Systematic Reviews as TopicSubject(s)
Anti-Infective Agents, Local/adverse effects , Betamethasone Valerate/administration & dosage , Cheilitis/drug therapy , Dermatitis, Allergic Contact/drug therapy , Eczema/drug therapy , Fusidic Acid/administration & dosage , Onychomycosis/drug therapy , Tea Tree Oil/adverse effects , Administration, Topical , Anti-Infective Agents, Local/therapeutic use , Betamethasone Valerate/therapeutic use , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/etiology , Female , Fusidic Acid/therapeutic use , Humans , Middle Aged , Patch Tests , Plant Extracts/adverse effects , Tea Tree Oil/therapeutic useABSTRACT
This study evaluated the clinical, laboratory, microbiological, radiological and treatment characteristics of patients with early-onset and late-onset spinal implant-associated infections. Patients diagnosed with spinal implant-associated infection between 2015-2019 were prospectively included and treated according to a standardised algorithm. Infections were classified as early-onset (≤6 weeks) and late-onset (>6 weeks). Among 250 patients, 152 (61%) had early-onset and 98 (39%) had late-onset infection. Local inflammatory signs was the most common manifestation in early-onset infections (84%), whereas late-onset infections presented mainly with persisting or increasing local pain (71%). Sonication fluid was more often positive than peri-implant tissue samples (90% vs. 79%; P = 0.016), particularly in late-onset infections (92% vs. 75%; P = 0.005). Predominant pathogens were coagulase-negative staphylococci, Staphylococcus aureus and Cutibacterium spp. Debridement and implant retention was the most common surgical approach in early-onset infections (85%), whereas partial or complete implant exchange was mainly performed in late-onset infections (62%). Of the 250 patients, 220 (88%) received biofilm-active antibiotics, and median treatment duration was 11.7 weeks. Moreover, 49 patients (20%) needed more than one revision for infection and six patients (2.4%) died during hospital stay. Concluding, most spinal implant-associated infections were acquired during surgery and presented within 6 weeks of surgery. Infections presented mainly with local inflammatory signs in early-onset and with persisting or increasing pain in late-onset infections. Sonication was the most sensitive microbiological method, particularly in late-onset infections. Debridement and implant retention was used in well-integrated implants without loosening, independent of the time of infection onset.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Propionibacteriaceae/drug effects , Prosthesis-Related Infections/drug therapy , Spine/microbiology , Staphylococcus aureus/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Biofilms/drug effects , Biofilms/growth & development , Child , Cohort Studies , Doxycycline/therapeutic use , Female , Fusidic Acid/therapeutic use , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Propionibacteriaceae/growth & development , Prospective Studies , Prosthesis-Related Infections/microbiology , Quinolones/therapeutic use , Rifampin/therapeutic use , Spine/pathology , Staphylococcus aureus/growth & development , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Young AdultABSTRACT
Dear Editor, Folliculitis decalvans (FD) is a rare form of primary neutrophilic cicatricial alopecia. It is a highly distressing disease that affects young and middle-aged adults, with a slight male predominance (1). The most frequent clinical manifestations are follicular pustules and diffuse and perifollicular erythema that heal with centrifugal scarring. Follicular tufting, erosions, and hemorrhagic crusts can also be present, and this alopecia is most often located at the vertex and occipital area. Patients frequently complain about pain, itching, or burning sensations, and the involvement of other body areas is rare (2). The pathogenesis of this disease remains unclear. Staphylococcus aureus and other hair follicle bacteria can often be isolated from the pustules, suggesting the role of a bacterial infection in its etiology. A defect in the host's immune response can also be postulated by reports of familial cases and the appearance of FD in patients with immunity dysfunctions. Other mechanical factors have been suggested, such as structural abnormalities of the follicle or local inflammation (2). Management of this alopecia is difficult and its course is typically chronic and relapsing. The treatment aim is to stop inflammation and further irreversible destruction of hair follicles. Antibiotics remain the first-line therapy, due both to their anti-inflammatory and antimicrobial properties (1). Although topical fusidic acid is widely used as adjuvant treatment, there are few data regarding its oral use. We report a case of folliculitis decalvans successfully treated with oral fusidic acid. Our patient was a 41-year old Cape Verdean woman with a two month history of alopecia with painful, purulent discharge at the vertex of the scalp. The patient was diagnosed with human immunodeficiency virus type 1 (HIV-1) infection 5 years prior and was stable on her regimen of efavirenz, tenofovir, and emtricitabine, with undetectable viral load. She denied application of topical or capillary products. Dermatological examination revealed a patch of cicatricial alopecia with crusts and follicular pustules (Figure 1). Direct microscopic examination and mycological culture showed no fungal element. A diagnosis of folliculitis decalvans was established and the patient was started on oral fusidic acid at a dose of 500 mg three times a day. Betamethasone dipropionate 0.05% and salicylic acid 3% lotion as well as azelaic acid 5% lotion were also applied to the affected area once daily. After two months of treatment, the patient showed clinical improvement, with less erythema and suppuration of the affected scalp. A partial hair regrowth was noted, mainly at the periphery. Subsequently the patient maintained only topical therapy, and no recurrences were observed after 6-months of follow-up. Fusidic acid is useful in the treatment of skin and soft tissue infections, particularly those due to S. aureus, as shown by randomized controlled studies (3). The clinical efficacy of fusidic acid in the treatment of folliculitis decalvans has been reported previously. Bogg was the first to describe this useful effect (4). Sutter also reported good results with fusidic acid used both topically and orally (500 mg three times a day) (5). However, both failed to report the treatment duration or the outcome on discontinuation. Abeck described three patients that responded to a three week oral course of fusidic acid (500 mg three times a day) and to a maintenance treatment with zinc sulfate (4). During the following year, recurrence was observed in only one patient after ending zinc sulfate therapy. Oral antibiotics are frequently used to treat folliculitis decalvans. Tetracyclines and the combination of clindamycin with rifampicin are the most commonly used (2). However, the disease usually progresses when treatment is stopped. Fusidic acid is an anti-staphylococcal drug with few adverse effects. It is highly bioavailable orally, and has a long plasma half-life. Despite years of clinical use in numerous countries, resistance rates remain at low levels to date (6). Since clinical series or cases including ours have shown good results, this drug should not be forgotten when considering treatment options for folliculitis decalvans.
Subject(s)
Alopecia/drug therapy , Anti-Bacterial Agents/therapeutic use , Folliculitis/drug therapy , Fusidic Acid/therapeutic use , Adult , Alopecia/etiology , Alopecia/pathology , Female , Folliculitis/etiology , Folliculitis/pathology , HumansABSTRACT
Conjunctivitis is one of the most common ophthalmologic conditions in general medical practice. In most cases, it is self-limiting and do not require topical antibiotic therapy. In a retrospective, observational cohort study during 2013-2017 in a region in Sweden conjunctivitis was diagnosed in 32 000 cases in primary care. Antibiotics were prescribed in 66% of undefined and in 83% of purulent conjunctivitis. Fusidic acid was the most common medication with 81% followed by chloramphenicol with 17%. Although unnecessary, the treatment is probably harmless. Toxicity is uncommon and the cost is low. Increased consciousness of this issue may however decrease resistance to antibiotics and support evidence-based medical practice.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Conjunctivitis , Drug Prescriptions/statistics & numerical data , Guideline Adherence , Administration, Ophthalmic , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Chloramphenicol/administration & dosage , Chloramphenicol/therapeutic use , Conjunctivitis/drug therapy , Conjunctivitis/epidemiology , Conjunctivitis/therapy , Conjunctivitis, Allergic/drug therapy , Conjunctivitis, Allergic/epidemiology , Conjunctivitis, Allergic/therapy , Conjunctivitis, Bacterial/drug therapy , Conjunctivitis, Bacterial/epidemiology , Conjunctivitis, Bacterial/therapy , Drug Utilization , Fusidic Acid/administration & dosage , Fusidic Acid/therapeutic use , Humans , Infant , Infant, Newborn , Medical Overuse , Middle Aged , Practice Patterns, Physicians' , Primary Health Care , Sweden/epidemiology , Young AdultABSTRACT
Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 µg/liter, 14 µg/liter, 25 µg/liter, and 153 µg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Biofilms/drug effects , Biological Assay/methods , Dried Blood Spot Testing/methods , Prostheses and Implants/microbiology , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/microbiology , Adult , Chromatography, Liquid/methods , Ciprofloxacin/therapeutic use , Drug Monitoring/methods , Female , Fusidic Acid/therapeutic use , Hematocrit/methods , Humans , Male , Middle Aged , Reproducibility of Results , Rifampin/therapeutic use , Tandem Mass Spectrometry/methodsABSTRACT
The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including meticillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625µg/mL to 0.125µg/mL. In vivo, topical auranofin proved superior to conventional antimicrobials, including fusidic acid and mupirocin, in reducing the mean bacterial load in infected wounds in a murine model of MRSA skin infection. In addition to reducing the bacterial load, topical treatment of auranofin greatly reduced the production of inflammatory cytokines, including tumour necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) and monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid and vancomycin. Taken together, these results support that auranofin has potential to be repurposed as a topical antimicrobial agent for the treatment of staphylococcal skin and wound infections.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Auranofin/therapeutic use , Drug Repositioning , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Skin Infections/drug therapy , Staphylococcus epidermidis/drug effects , Animals , Biofilms/drug effects , Cell Line , Chemokine CCL2/biosynthesis , Drug Resistance, Multiple, Bacterial , Drug Therapy, Combination , Female , Fusidic Acid/therapeutic use , Humans , Interleukin-1beta/biosynthesis , Interleukin-6/biosynthesis , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Mupirocin/therapeutic use , Staphylococcal Skin Infections/microbiology , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
Fusidic acid is an oral antistaphylococcal antibiotic that has been used in Europe for more than 40 years to treat skin infections as well as chronic bone and joint infections. It is a steroidal antibiotic and the only marketed member of the fusidane class. Fusidic acid inhibits protein synthesis by binding EF-G-GDP, which results in the inhibition of both peptide translocation and ribosome disassembly. It has a novel structure and novel mode of action and, therefore, there is little cross-resistance with other known antibiotics. Many mutations can occur in the FusA gene that codes for EF-G, and some of these mutations can result in high-level resistance (minimum inhibitory concentration [MIC] > 64 mg/L), whereas others result in biologically unfit staphylococci that require compensatory mutations to survive. Low-level resistance (<8 mg/L) is more common and is mediated by fusB, fusC, and fusD genes that code for small proteins that protect EF-G-GDP from binding fusidic acid. The genes for these proteins are spread by plasmids and can be selected mostly by topical antibiotic use. Reports of resistance have led to combination use of fusidic acid with rifampin, which is superseded by the development of a new dosing regimen for fusidic acid that can be used in monotherapy. It consists of a front-loading dose to decrease the potential for resistance development followed by a maintenance dose. This dosing regimen is now being used in clinical trials in the United States for skin and refractory bone and joint infections.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Fusidic Acid/therapeutic use , Peptide Elongation Factor G/antagonists & inhibitors , Protein Synthesis Inhibitors/therapeutic use , Staphylococcal Infections/drug therapy , Acute Disease , Administration, Oral , Chronic Disease , Drug Resistance, Bacterial , Drug Therapy, Combination , Humans , Microbial Sensitivity Tests , Rifampin/therapeutic useABSTRACT
We report a case of multiple eruptive pyogenic granulomas after scalding. A 4-year-old girl developed papules and nodules within the scalded areas after a hot soup burn. Although the occurrence of pyogenic granulomas after trauma to the skin is common, multiple lesions of pyogenic granuloma secondary to scalding are rare.
Subject(s)
Burns/complications , Granuloma, Pyogenic/etiology , Skin Diseases/etiology , Child, Preschool , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/therapeutic use , Female , Fusidic Acid/administration & dosage , Fusidic Acid/therapeutic use , Granuloma, Pyogenic/diagnosis , Granuloma, Pyogenic/drug therapy , Humans , Skin Diseases/diagnosis , Skin Diseases/drug therapyABSTRACT
The spread of multidrug-resistant Acinetobacter baumannii (MDRAB) has led to the renaissance of colistin (COL), often the only agent to which MDRAB remains susceptible. Effective therapy with COL is beset with problems due to unpredictable pharmacokinetics, toxicity, and the rapid selection of resistance. Here, we describe a potent synergistic interaction when COL was combined with fusidic acid (FD) against A. baumannii. Synergy in vitro was assessed against 11 MDRAB isolates using disc diffusion, checkerboard methodology (fractional inhibitory concentration index [FICI] of ≤ 0.5, susceptibility breakpoint index [SBPI] of >2), and time-kill methodology (≥2 log10 CFU/ml reduction). The ability of FD to limit the emergence of COL resistance was assessed in the presence and absence of each drug alone and in combination. Synergy was demonstrated against all strains, with an average FICI and SBPI of 0.064 and 78.85, respectively. In time-kill assays, COL-FD was synergistic and rapidly bactericidal, including against COL-resistant strains. Fusidic acid prevented the emergence of COL resistance, which was readily selected with COL alone. This is the first description of a novel COL-FD regimen for the treatment of MDRAB. The combination was effective at low concentrations, which should be therapeutically achievable while limiting toxicity. Further studies are warranted to determine the mechanism underlying the interaction and the suitability of COL-FD as an unorthodox therapy for the treatment of multidrug-resistant Gram-negative infections.
Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/therapeutic use , Colistin/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Fusidic Acid/therapeutic use , Drug Synergism , Drug Therapy, Combination/methods , Humans , Microbial Sensitivity Tests/methodsABSTRACT
OBJECTIVES: Increasing multidrug resistance amongst canine pathogenic staphylococci has renewed interest in topical antibacterial therapy for skin infections in the context of responsible veterinary prescribing. We therefore determined the activity in vitro of three clinically relevant topical agents and synergism between two of them against Staphylococcus pseudintermedius and Staphylococcus aureus. METHODS: The MICs of fusidic acid (nâ=â199), chlorhexidine (nâ=â198), miconazole (nâ=â198) and a 1:1 combination of miconazole/chlorhexidine (nâ=â198) were determined for canine isolates [50 MRSA and 49 methicillin-resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S. pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were calculated to assess the interaction of miconazole with chlorhexidine. RESULTS: MICs of each drug/combination were significantly (Pâ<â0.0005) higher for S. aureus when compared with S. pseudintermedius. Most strains (nâ=â172) had an MIC of fusidic acid of ≤0.03 mg/L (MIC ≥64 mg/L, nâ=â5 MRSA). All strains had MICs of chlorhexidine of 0.5-4 mg/L, except for one MRSA (MICâ=â8 mg/L). All but four strains had MICs of miconazole of 1-4 mg/L (MICâ=â16 mg/L, nâ=â3; MICâ=â256 mg/L, nâ=â1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against 49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP. CONCLUSIONS: Since the majority of these staphylococci, including methicillin-resistant isolates, had MICs that should be readily exceeded by topical skin application of these agents, their therapeutic efficacy for canine superficial pyoderma should be assessed. The synergistic interaction shown in vitro supports further clinical evaluation of miconazole/chlorhexidine combination therapy for staphylococcal infection.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chlorhexidine/pharmacology , Dog Diseases/microbiology , Fusidic Acid/pharmacology , Miconazole/pharmacology , Staphylococcal Skin Infections/microbiology , Staphylococcus/drug effects , Administration, Topical , Animals , Anti-Bacterial Agents/therapeutic use , Chlorhexidine/therapeutic use , Dog Diseases/drug therapy , Dogs , Drug Synergism , Fusidic Acid/therapeutic use , Germany , Miconazole/therapeutic use , Microbial Sensitivity Tests , Pyoderma/drug therapy , Pyoderma/microbiology , Staphylococcal Skin Infections/drug therapy , Staphylococcus/isolation & purification , United KingdomABSTRACT
Fusidic acid is a bacteriostatic antibiotic that inhibits the growth of bacteria by preventing the release of translation elongation factor G (EF-G) from the ribosome. The apicomplexan parasite Toxoplasma gondii has an orthologue of bacterial EF-G that can complement bacteria and is necessary for parasite virulence. Fusidic acid has been shown to be effective in tissue culture against the related pathogen Plasmodium falciparum, and current drug treatments against T. gondii are limited. We therefore investigated the therapeutic value of fusidic acid for T. gondii and found that the drug was effective in tissue culture, but not in a mouse model of infection. To determine whether this trend would occur in another intracellular pathogen that elicits a T helper 1-type immune response, we tested the efficacy of fusidic acid for the bacterium Listeria monocytogenes. Similar to its effects on T. gondii, fusidic acid inhibits the growth of L. monocytogenes in vitro, but not in mice. These findings highlight the necessity of in vivo follow-up studies to validate in vitro drug investigations.
Subject(s)
Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Fusidic Acid/pharmacology , Fusidic Acid/therapeutic use , Listeria monocytogenes/drug effects , Toxoplasma/drug effects , Animal Structures/microbiology , Animal Structures/parasitology , Animals , Colony Count, Microbial , Disease Models, Animal , Listeriosis/drug therapy , Mice , Microbial Sensitivity Tests , Parasitic Sensitivity Tests , Plasmodium falciparum , Survival Analysis , Toxoplasmosis, Animal/drug therapy , Treatment FailureABSTRACT
Meticillin-resistant Staphylococcus aureus (MRSA) is a rapidly spreading pathogen associated predominantly with skin infections. The lack of clinical evidence indicating the best treatment strategy to combat MRSA skin infections prompted us to investigate the efficacy of available treatment options in an experimental skin wound infection model in mice. Mice were treated either topically with retapamulin (1%), fusidic acid (2%) or mupirocin (2%) or systemically with linezolid (50-100 mg/kg/day) or vancomycin (50-200 mg/kg/day) twice daily for 3 days or 6 days and the total bacterial loads in the skin lesions were determined. Retapamulin, fusidic acid and mupirocin treatment for 3 days reduced the bacterial loads by 2.5, 2.9 and 2.0 log(10) CFU, respectively, and treatment for 6 days by 5.0, 4.2 and 5.1 log(10) CFU, respectively, compared with non-treated controls (P < 0.001). Systemic treatment with linezolid for 6 days reduced the bacterial loads by 1.6 log(10) CFU compared with non-treated mice (P < 0.001), whereas vancomycin treatment showed no effect on reducing the bacterial loads in infected skin lesions. These findings suggest that topical treatment with retapamulin and mupirocin is significantly more effective than systemic treatment with linezolid and vancomycin in eradicating MRSA in skin wounds. Retapamulin and mupirocin may provide an alternative to fusidic acid treatment of MRSA in skin wounds when resistance to fusidic acid is suspected.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents, Local/therapeutic use , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Skin Infections/drug therapy , Wound Infection/drug therapy , Acetamides/therapeutic use , Animals , Bacterial Load/drug effects , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Diterpenes , Female , Fusidic Acid/therapeutic use , Linezolid , Mice , Mice, Inbred BALB C , Microbial Sensitivity Tests , Mupirocin/therapeutic use , Oxazolidinones/therapeutic use , Vancomycin/therapeutic use , Wound Infection/microbiologyABSTRACT
There is a lack of surveillance data on resistance to fusidic acid (FA) in Asia, and no reviews of FA usage for the treatment of orthopaedic infections have been conducted since the year 2000. In this study, we present a systemic literature review of FA resistance in Asia and the clinical use of FA for the treatment of bone and joint infections (BJIs). The in vitro activity of FA against meticillin-resistant Staphylococcus aureus (MRSA) isolates remains good, with low (<10%) resistance rates in most Asian countries. FA in Asia appears to be a better oral anti-MRSA agent than trimethoprim/sulfamethoxazole and clindamycin. More than 80 cases of FA use for BJI have been reported since 2000 and the recurrence or failure rate is <10%. There is much evidence supporting the use of FA in combination with other antibiotics (e.g. rifampicin) as an oral treatment following intravenous glycopeptide treatment for BJIs.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bone Diseases, Infectious/drug therapy , Fusidic Acid/therapeutic use , Joint Diseases/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Acetamides/administration & dosage , Acetamides/therapeutic use , Anti-Bacterial Agents/administration & dosage , Asia , Bone Diseases, Infectious/epidemiology , Bone Diseases, Infectious/microbiology , Doxycycline/administration & dosage , Doxycycline/therapeutic use , Drug Resistance, Bacterial , Fusidic Acid/administration & dosage , Humans , Joint Diseases/epidemiology , Joint Diseases/microbiology , Linezolid , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Oxazolidinones/administration & dosage , Oxazolidinones/therapeutic use , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiologyABSTRACT
A short cut review was carried out to establish whether fucidic acid was as good as chloramphenicol in curing neonatal sticky eyes. 53 papers were found using the reported searches, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. It is concluded that fucidic acid drops have an equivalent cure rate to chloramphenicol drops in neonates with sticky eyes.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Chloramphenicol/therapeutic use , Conjunctivitis/drug therapy , Fusidic Acid/therapeutic use , Evidence-Based Medicine , Female , Humans , Infant, Newborn , Male , OintmentsABSTRACT
INTRODUCTION: In Greece, fusidic acid and clindamycin are commonly used for the empiric therapy of suspected staphylococcal infections. METHODS: The medical records of children examined at the outpatient clinics or admitted to the pediatric wards of the University General Hospital of Larissa, Central Greece, with community-associated staphylococcal infections from January 2003 to December 2009 were reviewed. RESULTS: Of 309 children (0-14 years old), 21 (6.8%) had invasive infections and 288 (93.2%) skin and soft tissue infections (SSTIs). Thirty-five patients were ≤30 days of age. The proportion of staphylococcal infections caused by a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate increased from 51.5% (69 of 134) in 2003-2006 to 63.4% (111 of 175) in 2007-2009 (P = 0.037). Among the CA-MRSA isolates, 88.9% were resistant to fusidic acid, 77.6% to tetracycline, and 21.1% to clindamycin. Clindamycin resistance increased from 0% (2003) to 31.2% (2009) among the CA-MRSA isolates (P = 0.011). Over the 7-year period, an increase in multidrug-resistant CA-MRSA isolates was observed (P = 0.004). One hundred and thirty-one (93.6%) of the 140 tested MRSA isolates were Panton-Valentine leukocidin-positive. Multilocus sequence typing of 72 CA-MRSA isolates revealed that they belonged to ST80 (n = 61), ST30 (n = 6), ST377 (n = 3), ST22 (n = 1), and ST152 (n = 1). Resistance to fusidic acid was observed in ST80 (58/61), ST30 (1/6), and ST22 (1/1) isolates. CONCLUSION: In areas with high rate of infections caused by multidrug-resistant CA-MRSA isolates, predominantly belonging to the European ST80 clone, fusidic acid and clindamycin should be used cautiously as empiric therapy in patients with suspected severe staphylococcal infections.
Subject(s)
Clindamycin/therapeutic use , Community-Acquired Infections/microbiology , Fusidic Acid/therapeutic use , Methicillin-Resistant Staphylococcus aureus/classification , Staphylococcal Infections/epidemiology , Adolescent , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Drug Resistance, Multiple, Bacterial , Female , Genotype , Greece/epidemiology , Humans , Infant , Infant, Newborn , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phenotype , Staphylococcal Infections/drug therapyABSTRACT
We report a case of infective endocarditis due to vancomycin-intermediate Staphylococcus aureus (VISA). This was treated with a combination of intravenous linezolid and fusidic acid. Cure was achieved without surgical intervention.
Subject(s)
Acetamides/therapeutic use , Endocarditis, Bacterial/drug therapy , Oxazolidinones/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Acetamides/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Echocardiography , Endocarditis, Bacterial/diagnostic imaging , Endocarditis, Bacterial/microbiology , Fusidic Acid/administration & dosage , Fusidic Acid/therapeutic use , Humans , Injections, Intravenous , Linezolid , Male , Microbial Sensitivity Tests , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/microbiology , Oxazolidinones/administration & dosage , Staphylococcal Infections/diagnostic imaging , Staphylococcal Infections/microbiology , Staphylococcus aureus/isolation & purification , Vancomycin ResistanceABSTRACT
Los antibióticos tópicos ofrecen varias ventajas sobre los antibióticos sistémicos, tales como una menor capacidad de generar resistencia bacteriana, una concentración alta de la droga en el sitio de la infección, ausencia de efectos adversos y toxicidad sistémica y bajo costo. Los antibióticos locales son útiles en el tratamiento de las infecciones bacterianas superficiales menores, dermatosis o heridas secundariamente infectadas, eliminación del estado de portador nasal de S. aureus y tratamiento adyuvante de la antibiotioterapia sistémica en infecciones bacterianas superficiales más extensas. La dematitis de contacto alérgica y la resistencia bacteriana son los dos problemas principales en la antibioticoterapia tópica. El desarrollo de nuevos antibióticos con mecanismos de acción únicos es de importancia para la práctica diaria dermatológica
Topical antibiotics offer several advantages, such as decreased induction of bacterial resistance, high concentration of the drug in the site of infection, avoidance of systemic adverse effects or toxicity and low cost. Local antibiotics are useful in the treatment of minor superficial bacterial infections, secondarily infected dermatosis or wounds, elimination of S. Aureus from nasal mucosa, and adjuvant therapy when associated with systemic antibiotics for more extensive superficial bacterial infections. Contact allergic dermatitis and bacterial resistance are the two main problems in topical antibacterial treatment. Development of new antibiotics, with unique mode of action is crucial for dermatologists
Subject(s)
Humans , Fusidic Acid/therapeutic use , Anti-Bacterial Agents/therapeutic use , Impetigo , Mupirocin/therapeutic use , Neomycin/therapeutic use , Polymyxin B/therapeutic use , Silver Sulfadiazine/therapeutic useABSTRACT
Many recent studies have suggested that low-density lipoprotein (LDL) oxidation, endothelial dysfunction, and inflammation are involved in the pathogenesis of atherosclerosis. Herbal regimens in the treatment of blood stasis, a counterpart of atherosclerosis, commonly use medicinal plants of leguminosae and labiatae. We have developed disease-oriented screening methods to search for bioactive components, particularly isoflavones in leguminosae and polyphenols in labiatae from Chinese herbal medicines. Many bioactive components and active fractions capable of inhibiting a. Cu(II)-induced LDL oxidation, b. oxidized LDL-induced endothelial damage, c. uptake of oxidized LDL by macrophages (J774A.1), and d. expression of cell adhesion molecules (CAMs) have been identified. A polyphenol, namely salvianolic acid B from Salvia miltiorrhiza was identified to be a potent antioxidant, endothelial-protecting agent, and an inhibitor to suppress the expression of ICAM and VCAM. This review also briefly describes the strategy for developing herbal medicines as anti-atherosclerotic agents.