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Burn wounds are a major burden, with high mortality rates due to infections. Staphylococcus aureus is a major causative agent of burn wound infections, which can be difficult to treat because of antibiotic resistance and biofilm formation. An alternative to antibiotics is the use of bacteriophages, viruses that infect and kill bacteria. We investigated the efficacy of bacteriophage therapy for burn wound infections, in both a porcine and a newly developed human ex vivo skin model. In both models, the efficacy of a reference antibiotic treatment (fusidic acid) and bacteriophage treatment was determined for a single treatment, successive treatment, and prophylaxis. Both models showed a reduction in bacterial load after a single bacteriophage treatment. Increasing the frequency of bacteriophage treatments increased bacteriophage efficacy in the human ex vivo skin model, but not in the porcine model. In both models, prophylaxis with bacteriophages increased treatment efficacy. In all cases, bacteriophage treatment outperformed fusidic acid treatment. Both models allowed investigation of bacteriophage-bacteria dynamics in burn wounds. Overall, bacteriophage treatment outperformed antibiotic control underlining the potential of bacteriophage therapy for the treatment of burn wound infections, especially when used prophylactically., Competing Interests: The authors declare no conflict of interest. more...

Introduction: We investigated the prevalence of fusidic acid (FA) resistance in MSSA and MRSA stratified by sequence (ST) and spa types, and determined the prevalence of FA resistance mechanisms., Methods: From August 2014 to April 2020, S. aureus blood isolates were collected in Asan Medical Center, Seoul, South Korea. Antimicrobial susceptibility tests were performed using broth microdilution and interpreted according to EUCAST's FA criteria. We performed spa typing for fusA mutation presence and acquired FA resistance determinants (fusB, fusC, and fusD) by PCR., Results: Of the 590 MRSA isolates, 372 were FA resistant, and among 425 MSSA isolates, 136 were resistant. Of the 380 ST5-MRSA isolates, 350 were FA resistant, whereas only 1 of 14 ST5-MSSA isolates was FA resistant. Conversely, of the 163 ST72-MRSA isolates, only 8 were resistant, whereas 37 of 42 ST72-MSSA were resistant. The fusA mutation (80%) was the most common determinant. The one FA resistant ST5-MSSA isolate belonged to the t2460 spa type, the most common spa type (24 of 35 isolates) of FA resistant ST5-MRSA. In addition, t324 and t148, which are minor spa types of ST72-MSSA, were susceptible to FA, in contrast to other ST72-MSSA spa types, and the major spa type of ST72-MRSA (110 of 163 isolates)., Conclusions: FA resistance was common in ST5-MRSA and ST72-MSSA, and rare in ST5-MSSA and ST72-MRSA. Our findings suggest that minor clones of ST5-MSSA isolates, with the fusA mutation and minor clones of ST72-MSSA susceptible to FA, may have evolved to harbor the mecA gene., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.) more...

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with high levels of morbidity and is considered a difficult-to-treat infection, often requiring nonstandard treatment regimens and antibiotics. Since over 40% of the emerging antibiotic compounds have insufficient solubility that limits their bioavailability and thus efficacy through oral or intravenous administration, it is crucial that alternative drug delivery products be developed for wound care applications. Existing effective treatments for soft tissue MRSA infections, such as fusidic acid (FA), which is typically administered orally, could also benefit from alternative routes of administration to improve local efficacy and bioavailability while reducing the required therapeutic dose. Herein, we report an antimicrobial poly(oligoethylene glycol methacrylate) (POEGMA)-based composite hydrogel loaded with fusidic acid-encapsulating self-assembled polylactic acid- b -poly(oligo(ethylene glycol) methyl ether methacrylate) (PLA-POEGMA) nanoparticles for the treatment of MRSA-infected skin wounds. The inclusion of the self-assembled nanoparticles (380 nm diameter when loaded with fusidic acid) does not alter the favorable mechanical properties and stability of the hydrogel in the context of its use as a wound dressing, while fusidic acid (FA) can be released from the hydrogel over ∼10 h via a diffusion-controlled mechanism. The antimicrobial studies demonstrate a clear zone of inhibition in vitro and a 1-2 order of magnitude inhibition of bacterial growth in vivo in an MRSA-infected full-thickness excisional murine wound model even at very low antibiotic doses. Our approach thus can both circumvent challenges in the local delivery of hydrophobic antimicrobial compounds and directly deliver antimicrobials into the wound to effectively combat methicillin-resistant infections using a fraction of the drug dose required using other clinically relevant strategies. more...

There is currently no specific and effective treatment for bacteremia-mediated sepsis. Hence, this study engineered a combinatorial nanosystem containing neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles to enable the dual mitigation of bacteremia-associated inflammation and methicillin-resistant Staphylococcus aureus (MRSA) infection. The targeted nanoparticles were developed by conjugating anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibody fragment on the nanoparticulate surface. The particle size and zeta potential of the as-prepared nanosystem were about 200 nm and -25 mV, respectively. The antibody-conjugated nanoparticles showed a three-fold increase in neutrophil internalization compared to the unfunctionalized nanoparticles. As a selective phosphodiesterase (PDE) 4 inhibitor, the roflumilast in the nanocarriers largely inhibited cytokine/chemokine release from the activated neutrophils. The fusidic acid-loaded nanocarriers were vital to eliminate biofilm MRSA colony by 3 log units. The nanoparticles drastically decreased the intracellular bacterial count compared to the free antibiotic. The in vivo mouse bioimaging demonstrated prolonged retention of the nanosystem in the circulation with limited organ distribution and liver metabolism. In the mouse bacteremia model, the multifunctional nanosystem produced a 1‒2 log reduction of MRSA burden in peripheral organs and blood. The functionalized nanosystem arrested the cytokine/chemokine overexpression greater than the unfunctionalized nanocarriers and free drugs. The combinatory nanosystem also extended the median survival time from 50 to 103 h. No toxicity from the nanoformulation was found based on histology and serum biochemistry. Furthermore, our data proved that the active neutrophil targeting by the versatile nanosystem efficiently alleviated MRSA infection and organ dysfunction caused by bacteremia. STATEMENT OF SIGNIFICANCE: Bacteremia-mediated sepsis poses a significant challenge in clinical practice, as there is currently no specific and effective treatment available. In our study, we have developed a novel combinatorial nanosystem to address this issue. Our nanosystem consists of neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles, enabling the simultaneous mitigation of bacteremia-associated inflammation and MRSA infection. Our nanosystem demonstrated the decreased neutrophil activation, effective inhibition of cytokine release, elimination of MRSA biofilm colonies, and reduced intracellular bacterial counts. In vivo experiments showed prolonged circulation, limited organ distribution, and increased survival rates in a mouse bacteremia model. Importantly, our nanosystem exhibited no toxicity based on comprehensive assessments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.) more...

Acute lung injury (ALI) are severe forms of diffuse lung disease that impose a substantial health burden all over the world. In the United States, approximately 190,000 cases per year of ALI each year, with an associated 74,500 deaths per year. Anti-inflammatory therapy has become a reasonable approach for the treatment of patients with ALI. In this study, fusidic acid derivatives were used to design new anti-inflammatory compounds with high pharmacological activity and low toxicity. A total of 30 new fusidic acid derivatives were discovered, synthesized, and screened for their anti-inflammatory activity against lipopolysaccharide (LPS)-treated RAW264.7 cells. Of them, b2 was found to be the most active, with a higher efficiency compared with fusidic acid and celecoxib in 10 μM. In vitro, we further measured b2 inhibited inflammatory factor NO (IC 50  = 5.382 ± 0.655 μM), IL-6 (IC 50  = 7.767 ± 0.871 μM), and TNF-α (IC 50  = 7.089 ± 0.775 μM) and b2 inhibited inflammatory cytokines COX-2 and iNOS, ROS production, NF-κB/MAPK and Bax/Bcl-2 signaling pathway pathway. In vivo,b2 attenuated ALI pathological changes and inhibited inflammatory cytokines COX-2 and iNOS in lung tissue and NF-κB/MAPK and Bax/Bcl-2 signaling pathway. In conclusion, b2 may be a promising anti-inflammatory lead compound., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.) more...

The literature on fusidic acid resistant Staphylococcus aureus strains is scarce in Iran, although the emergence of these strains in health care settings is increasing. This descriptive cross-sectional study was conducted on 68 fusidic acid resistant S. aureus strains to learn about the molecular characteristics and antimicrobial resistance of strains isolated from hospitalized patients. In the present study, the prevalence of resistance to fusidic acid in S. aureus isolates was 15.1%. Fusidic acid resistance determinative factors (fusB, fusC and fusD) were identified by multiplex PCR assay. To detect the existence of fusA and fusE determinants and their mutation status, amplifications and sequencing were performed. Molecular characterization of fusidic acid resistant isolates was investigated by SCCmec and spa typing methods. All strains were MRSA and multi drug resistant. Two (2.9%) and 31 (45.6%) isolates were resistant to vancomycin and mupirocin respectively. The SCCmec type IV was highly prevalent representing 50% followed by types III (51.5%), and SCCmec types II (13.2%). fusB, was the most predominant acquired gene (66.2%) followed by fusC (19.1%), and fusA (14.7%). The mutations in fusA were present in 10 isolates with 5 (50%) having L461K mutation showing fusidic acid MIC values of ≥256 μg ml-1 followed by H457Y (40%), and H457Q (10%) showing fusidic acid MIC values of 128 and 64 μg ml-1 respectively. Isolates were allocated to ten particular t030 (22.1%), t037 (14.6%), t408 (11.8%), t064 (11.8%), t008 (10.3%), t002 (8.8%), t005 (5.9%), t790 (5.9%), t318 (4.4%), and t018 (4.4%) spa types. fusA positive isolates were assigned to particular spa types t002 (60%), and t005 (40%). There may be be a spreading of fusidic acid resistance among MRSA, creating worrying public concern. This research notes the importance of adequate data of local prevalence of FA-resistant MRSA in Iran for taking appropriate measures to treat, control and reduce the incidence of these isolates. more...

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., (© 2022 S. Karger AG, Basel.) more...

Sepsis is often caused by systemic inflammatory responses. Stimulator of interferon genes (STING) could be a promising treatment target for sepsis. In this study, we report the design and synthesis of a new series of fusidic acid derivatives. Among the synthesized derivatives, the promising compound 30 inhibited lipopolysaccharide (LPS)-induced nitric oxide production in macrophages with an IC 50 of 1.15 μM. Compound 30 was then identified as a STING inhibitor that suppressed LPS-induced inflammatory responses and inhibited the abnormal activation of the TBK1, IRF3, and NF-κB signaling pathways by targeting STING. In vivo treatment with compound 30 significantly inhibited the inflammatory response and ameliorated the histopathological changes of the liver, and the mechanism of its anti-inflammatory effect in vivo was the same as that in vitro. Our studies identified compound 30 as a potent STING inhibitor, laying the groundwork for future drug development of anti-inflammatory agents for the treatment of sepsis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.) more...

Objectives: Prevalence of MRSA in patients with CF has risen over the past decades, and chronic infection with MRSA is associated with worse outcome in this patient group., Methods: This retrospective observational study investigated long-term eradication rate in pediatric and adult CF patients with chronic MRSA infection, using a 6-month eradication regimen containing 2 oral antibiotics, combined with topical decolonisation measures. Respiratory tract cultures were performed at least every three months, from the first MRSA-positive culture onwards., Results: A total of 24 patients with chronic MRSA infection were identified from our CF patient registry, of which 13 patients underwent an eradication attempt. The regimen consisted of 2 oral antibiotics: a combination of rifampicin, fusidic acid, clindamycin and co-trimoxazol, based on the sensitivity pattern of the MRSA strain. At the end of the study period (median 8.2 years), 12 out of 13 patients (92%) were MRSA negative. None of the patients interrupted treatment due to side-effects., Conclusions: Eradication of chronic MRSA infection is feasible, well-tolerated and highly successful, and can offer a long-lasting MRSA-negative status, obviating the need for patient segregation. more...

In this retrospective observational study, we analysed a community outbreak of impetigo with meticillin-resistant Staphylococcus aureus (MRSA), with additional resistance to fusidic acid (first-line treatment). The outbreak occurred between June 2018 and January 2020 in the eastern part of the Netherlands with an epidemiological link to three cases from the north-western part. Forty nine impetigo cases and eight carrier cases were identified, including 47 children. All but one impetigo case had community-onset of symptoms. Pharmacy prescription data for topical mupirocin and fusidic acid and GP questionnaires suggested an underestimated outbreak size. The 57 outbreak isolates were identified by the Dutch MRSA surveillance as MLVA-type MT4627 and sequence type 121, previously reported only once in 2014. Next-generation sequencing revealed they contained a fusidic acid resistance gene, exfoliative toxin genes and an epidermal cell differentiation inhibitor gene. Whole-genome multilocus sequence typing revealed genetic clustering of all 19 sequenced isolates from the outbreak region and isolates from the three north-western cases. The allelic distances between these Dutch isolates and international isolates were high. This outbreak shows the appearance of community-onset MRSA strains with additional drug resistance and virulence factors in a country with a low prevalence of antimicrobial resistance. more...

Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO®) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin® cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) more...

Objectie To investigate the susceptibility of drug-resistant staphylococci isolated from different parts of the anterior segment to levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin. Methods: Experimental Study. A total of 67 patients with anterior segment infection (33 cases of conjunctivitis, 6 cases of bacterial keratitis, 7 cases of blepharitis, 9 cases of neonatal dacryocystitis, 9 cases of neonatal dacryocystitis, 1 case of adult dacryocystitis and 11 cases of other infectious eye diseases) were collected from the conjunctival sac, cornea, eyelid margin and lacrimal sac. Minimum inhibitory concentration (MIC) determination of methicillin-resistant Staphylococcus (MRS) strains and β-lactamase-producing (β-Lac) strains by a micro-liquid-based method, according to the M100 standard of the American Institute for Clinical and Laboratory Standardization Susceptibility and resistance determinations were made. Data were statistically analyzed using Chi-square or Fisher's exact test. Results: Thirty-five MRS, 30 β-Lac and 2 β-Lac MRS isolates were identified from 67 multidrug-resistant Staphylococcus . There were 3, 9, 4, and 19 MRS isolates isolated from the lacrimal sac, cornea, eyelid margin and conjunctival sac, accounting for 3/4, 9/12, 4/8, 19/43 (44.2%) of the isolated sites respectively. There were 1, 3, 3, and 23 β-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of β-Lac isolates isolated from patients with a diagnosis of conjunctivitis was 17 (25.3%) from the conjunctival sac. Among the MRS strains isolated from the cornea and lacrimal sac, 5 (7.5%) and 3 (4.5%) were from patients diagnosed with bacterial keratitis and neonatal tear, respectively. The number of MRS strains and β-Lac isolates isolated from patients with a diagnosis of blepharitis were both 3 (4.5%) from the lid margin.Among the strains isolated from the eyelid margin and the conjunctival sac, drug-resistant Staphylococcus epidermidis was the main strain, the drug-resistant Staphylococcus aureus was the major isolates in lacrimal sac and cornea. Among the 35 MRS isoaltes, 25, 24, 12, 12, and 11 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, clindamycin and tobramycin, and the sensitivity rates were 71.4%, 68.6%, 34.3%, 34.3% and 31.4%, the difference was statistically significant ( χ 2 =22.756, P< 0.001), The sensitivity rates of levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin against MRS isolates from the anterior segment were both statistically significant differences ( χ 2 =18.493, 11.594, 8.906, 9.841, 16.059; all P< 0.05). The susceptibility rates of MRS isolates against five antibiotics was statistically significant differences ( χ 2 =33.080, P< 0.001). Among the 30 β-Lac isolates, 27, 22, 19, 16, and 8 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, tobramycin and clindamycin, and the sensitivity rates were 90.0 % , 73.3%, 63.3%, 53.3% and 26.7%, the difference was statistically significant ( χ 2 =28.280, P< 0.001). The sensitivity rates of five antibiotics against β-Lac isolates from the anterior segment were both statistically significant differences ( χ 2 =50.971, 24.543, 48.147, 44.899, 18.676; all P< 0.001). The susceptibility rates of β-Lac isolates against five antibiotics was statistically significant differences ( χ 2 =23.383, P< 0.001). The sensitivity of cefazolin sodium and fusidic acid against β-Lac isolates were higher than MRS isolates. Conclusions: Cefazolin sodium and fusidic acid may be the best choice for the treatment of drug-resistant Staphylococcus isolated from anterior conjunctival sac, cornea, eyelid margin and lacrimal sac, especially for β-Lac-producing drug-resistant Staphylococcus infection. more...

Adverse drug reactions of broad-spectrum fluoroquinolones or rifampicin are not uncommon during osteomyelitis and orthopaedic implant infections (OOII). Thus, we made an overview (i) of the prescription of fusidic acid (FA) and (ii) of FA susceptibility of Staphylococcus sp. and Cutibacterium sp. strains isolated from bone samples. All prescriptions of FA and all bone samples with positive culture for Staphylococcus sp. or Cutibacterium sp. (Reims University Hospital June 2017-May 2021) were included. All Staphylococcus aureus strains were considered as significant, whereas Coagulase-negative Staphylococcus and Cutibacterium spp. strains were not if these strains grew only on one sole sample. The antibiotic susceptibility of Staphylococcus sp. strains and the susceptibility to FA of Cutibacterium sp. strains had been determined using disk diffusion methods, as described for Staphylococcus sp. in the CASFM/EUCAST guidelines. The mean FA consumption was 0.6 daily defined doses/1000 patient days. FA was prescribed for OOII due to Staphylococcus sp. and Cutibacterium sp. in 24 and 2 cases, respectively. Among 401 Staphylococcus sp. strains, there were 254 S. aureus (63.3%), 84 methicillin-resistant (20.9%) and 333 FA-susceptible (83.0%) strains. S. aureus and methicillin-sensitive strains were more likely to be susceptible to FA (p < 0.001). Among 39 Cutibacterium sp. strains, the FA inhibition zone diameter geometric mean was 28.6 mm (24-35 mm), suggesting that all these strains could be considered as susceptible to FA. These data suggested that FA could be more frequently used in OOII due to Staphylococcus sp. and Cutibacterium sp., subject to the absence of other resistant bacteria., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Introduction: Scabies is caused by Sarcoptes scabiei var hominis, often causing secondary bacterial infections, especially by Streptococcus pyogenes and Staphylococcus aureus. Permethrin 5% cream is the first-line of treatment that is recommended, combined with Fusidic acid 2% cream as the first-line topical antibiotic. We investigated the efficacy of a combination of permethrin 5% cream and fusidic acid 2% cream for the treatment of impetiginized scabies., Methodology: A double-blind, randomized clinical trial was organized at two Islamic boarding schools in Bogor, West Java, Indonesia. Forty subjects were randomly allocated into the intervention group (permethrin 5% and fusidic acid 2%; n = 20), and the control group (permethrin 5% and placebo; n = 20). Treatment efficacy was determined through the visual analogue scale (VAS) for pruritus and pain, and by examining bacterial cultures., Results: Treatment efficacy in the intervention group was higher than in the control group on day 7 (80% vs. 35%) and day 14 (95% vs 35%, p ≤ 0.001, RR 2.714) with decreasing VAS for pruritus (p = 0.04) and pain (p = 0.035). The most common bacterium was Staphylococcus aureus. Some minor adverse effects such as itch and heat occurred temporarily., Conclusions: Treating impetiginized scabies with permethrin 5% and fusidic acid 2% cream is more effective than treating with only 5% premethrin. The most common bacterium causing secondary infection in impetiginized scabies is Staphylococcus aureus., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Aninda Marina, Sri Linuwih Menaldi, Endi Novianto, Sandra Widaty.) more...

Introduction and Aim: Multidrug resistance in bacteria has become a widespread scourge. The objective of this study is to investigate the epidemiology of multidrug-resistant bacteria (MDR) at Fattouma Bourguiba University Hospital of Monastir - Tunisia compared to the community and to define their antibiotic resistance profiles., Methods: It was a retrospective and descriptive study over a period of 5 years (2016-2020) conducted at the microbiology department of Fattouma-Bourguiba University Hospital of Monastir - Tunisia. All MDR strains isolated from diagnostic microbiological samples collected from patients hospitalized in high-risk infectious departments and from outpatients were included in our study., Results: A total of 4324 MDR among 16353 bacteria were isolated during the study period, i.e. a resistance rate of 26.4% with a predominance of hospital strains (80.3% versus 19.7% in the city). Third generation cephalosporin-resistant Enterobacteriaceae were the most prevalent and were mainly represented by extended-spectrum beta- lactamases (67.1% versus 83.4% in the community). Escherichia coli was the most frequent species (40.9%). It was frequently associated with resistance to fluoroquinolones (in more than 73% of cases). Imipenem-resistant Acinetobacter baumannii was mostly responsible for hospital acquired infections (77%). Co- resistances concerned most of the antibiotics but spared colistin. Methicillin-resistant Staphylococcus aureus infections were more frequent in the city (20.5% versus 19.3% in hospitals). Resistance associated was mainly to fusidic acid (49.6%). Glycopeptides have maintained their activity and only 2% were of decreased sensitivity to vancomycin., Conclusion: The emergence of MDR always represents a public health challenge. Thus, hygiene measures associated with an optimization of antibiotic therapy are necessary for a better control of their diffusion. more...

Aim: To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance., Methodology: This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method., Results: The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01)., Conclusions: The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy., Competing Interests: FCNK and M-MO are affiliated with FleRhoLife Research Consult, but this firm didnot provide financial support nor play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. more...

Scleredema adultorum of Buschke is a rare disorder of the connective tissue, involving the skin. Here, we present a 61-year-old male, who is a known case of compensated liver cirrhosis with a past history of being treated for autoimmune thyrotoxicosis, who presented with complaints of alopecia, skin tightening, dry skin, pruritus, and woody indurated plaques on the skin of the upper back, shoulder, and arms. Skin biopsy of the arm revealed the characteristic features of scleredema. He was extensively evaluated for known literature-cited causes of scleredema, and the work up revealed a negative result. He was also found to be hypothyroid on presentation. Hence, we present a case of scleredema occurring in a patient with hypothyroidism and chronic liver disease, which to our knowledge is being described for the first time in literature., Competing Interests: None more...

Background: Inflammation and postinflammatory hyperpigmentation (PIH) are two adverse side effects of ablative fractional CO 2 laser (ablative Fr CO 2 ) treatment for both rejuvenation and acne scars., Aims: To evaluate the efficacy of fusidic acid cream versus erythromycin ointment as postoperative therapy in patients who underwent ablative Fr CO 2 treatment for atrophic acne scars., Methods: Sixty Chinese patients who fulfilled the study criteria were recruited and randomly assigned to an experimental group treated with fusidic acid cream or a control group treated with erythromycin ointment. Postoperative treatment lasted for 7 days in each group. Each patient had two follow-up visits at 8 and 12 weeks. In total, three patients dropped out of the study, one in the experimental group at week 8 and two in the control group at weeks 8 and 12. Baseline and postoperative inflammation and PIH were assessed by facial examination, photographs, and questionnaires. Besides, PIH was evaluated by the Hyperpigmentation Activity and Severity Index (HASI) and a five-point grading system., Results: Moderate-to-severe PIH was observed in both groups. However, the mean HASI score and severity of PIH in the experimental group were lower than those of the control group at weeks 8 and 12 (P < 0.05). In the control group, one patient developed postoperative abscesses and one had papules, whereas no inflammation was observed in the experimental group participants., Conclusion: Fusidic acid cream shows promise as a common treatment after ablative Fr CO 2 therapy to reduce postoperative inflammation and PIH., (© 2020 Wiley Periodicals LLC.) more...

Competing Interests: The authors have no funding or conflicts of interest to declare.

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. more...

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...

Erosive pustular dermatosis of the scalp is a slowly progressive chronic inflammatory disease that predominantly affects elderly male patients with marked actinic damage. The clinical evolution consists firstly of keratotic and erosive plaques surmounted by yellow-brown crusts and non-follicular pustules; later, the active crusting lesions regress in number and the scarring process causes diffuse cutaneous thinning and loss of hair follicles. However, manifestations may be atypical, leading to frequent misdiagnosis. We present a case series of post-traumatic erosive pustular dermatosis on the scalp of 4 elderly patients. The characterising feature was the presence of erosion consisting of abundant hypergranulation tissue, with an almost total lack of crusts and pustules. Dermoscopy showed a unique pattern of stretched and dilated linear, telangiectatic and polymorphous on-focus vessels, milky-red areas and white scarring areas. This clinical entity is rarely reported in the literature. The majority of reported cases were located on the legs., (© 2019 The Australasian College of Dermatologists.) more...

Background : Idiopathic facial aseptic granuloma (IFAG) is a rare skin disease that typically presents in children with one or more nontender, erythematous to violaceous nodules located on the cheeks or eyelids. Lesions are not accompanied by other skin abnormalities. IFAG remains a diagnostic challenge in pediatric dermatology, because several diseases may present with similar signs. Case presentation : A three-year-old girl with a previous negative clinical history was referred to our hospital for the evaluation of some asymptomatic nodules on the convexity of the left cheek. The nodules had appeared two months before, and had gradually increased in size. Her mother denied any association with trauma or insect bites. The nodules had a hard-elastic consistency, were moderately firm, and were not fluctuant. No associated lymphadenopathy was observed. The girl was afebrile and in good general condition. A histologic evaluation of a biopsy specimen revealed an inflammatory, granulomatous-diffuse infiltrate in the superficial and deep dermis consisting of giant cells, histiocytes, lymphocytes, neutrophils, eosinophils, and plasma cells. The Ziehl-Neelsen stains, Gram-stains, and cultures were negative. Suspecting an IFAG, treatment with topical fusidic acid and oral clarithromycin for 14 days was started. After two months, the lesion resolved and did not recur. Conclusion : This case shows how to differentiate IFAG from other dermatologic diseases associated with a negative evolution. Treatment with oral clarithromycin was effective in our patient. However, more scientific evidence is needed to evaluate the most suitable antibiotic therapy. Further studies are also needed to establish whether antibiotics actually impact IFAG prognosis. more...

Competing Interests: Competing interests: None declared.

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. more...

A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC 50 values in the range of 1.26-3.57 μM. Further research revealed that compound 4 induced Hela cells to undergo apoptosis by increasing the ratio of the cells in the Sub-G 0 /G 1 phase via decreasing the neo-synthesized proteins in a dose-dependent manner from 1 to 10 μM. Compound 4 also showed good in vivo anti-tumor activity against the xenograft tumor of Hela cells and had no apparent toxicity. This study highlights the advantage of introducing the medium-length amino-terminal groups at the 3-OH position of FA to enhance its anti-tumor activity and suggests that compound 4 provides a starting point for designing more potent derivatives in the future., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.) more...

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. more...

Background: Trichloroacetic acid (TCA) is a nontoxic chemical that has been used for more than 20 years in skin rejuvenation treatments for various skin conditions. Currently, there is no single accepted protocol for local burn care following TCA peeling., Objective: This pilot study assesses the efficacy and tolerability of a silver-based gel compared with fusidic acid cream as a complementary topical treatment for burns following TCA peeling., Materials and Methods: The authors conducted a comparative study on healthy female patients in the Department of Plastic and Reconstructive Surgery at Assaf Harofe Medical Center (Zerifin, Israel). Patients were treated with TCA 15% for superficial facial skin peeling, followed by applications of both the silver-based gel and fusidic acid cream on opposite sides of their face. Patient evaluation included high-resolution photographic evaluation pre- and post-peeling; physician assessment for the presence of complications such as infection, edema, and allergic reactions; and a self-completed questionnaire in reference to the outcomes and side effects (eg, burning, itching) experienced., Results: Seventeen women were included in the study. None of the patients experienced an infection or allergic reaction. Photographic analysis found no significant differences in the outcomes between topical treatments, with a trend for better results with the silver-based gel. Pain, edema, and burning sensations were not significantly different between the topical treatments. Itching was less prevalent in the silver-based gel group (P = .046)., Conclusions: Comparing between the groups treated with silver-based gel and fusidic acid cream, the authors found no inferiority in the outcomes or the prevalence of any complaints, and a superior effect on the prevention of wound itch using a silver-based gel. more...

Condyloma acuminatum (CA), or genital wart, is a sexually transmitted infection caused by human papillomaviruses. Increasing evidences demonstrated that photodynamic therapy (PDT) is effective in eliminating latent HPV infection, the major reason for CA recurrence. We observed an increasing number of infections after PDT in CA patients, which has not been reported before. This study aims to evaluate the incidence and management of infection in CA patients after PDT procedure. CA patients received PDT from January 2015 to February 2016 at the outpatient setting. Patients were randomly divided into two groups: the control group and fusidic acid group. Patients in the fusidic acid group used topical fusidic acid (2%) and recombinant human interferon after 5-aminolevulinic acid (ALA)-PDT procedure, while patients in the control group only used recombinant human interferon. Patients came to our department for follow-up evaluations at 4, 8, and 12 weeks after treatment for three times of PDT. Patients with ALA-PDT-associated infection were then randomly divided into two groups: the fusidic acid group and mupirocin group. During the 13-month study period, a total of 718 patients with 2154 times of PDT procedures were enrolled. The infection rate after PDT was 8.5% in the control group, while it was 1.1% in the prophylactic topical fusidic acid group. The cure rate of PDT-associated infection was 85.7% in the fusidic acid group and 86.7% in the mupirocin group. In conclusion, prophylactic topical antibiotic was useful for reduction of PDT-associated infection and optimal wound healing in CA patients. more...

Following a severe case of rhabdomyolysis in our University Hospital after a co-administration of atorvastatin and fusidic acid, we describe this interaction as this combination is not clearly contraindicated in some countries, particularly for long-term treatment by fusidic acid. All cases of rhabdomyolysis during a co-administration of a statin and fusidic acid were identified in the literature and in the World and Health Organization database, VigiBase ® . In the literature, 29 cases of rhabdomyolysis were identified; mean age was 66 years, median duration of co-administration before rhabdomyolysis occurrence was 21 days, 28% of cases were fatal. In the VigiBase ® , 182 cases were retrieved; mean age was 68 years, median duration of co-administration before rhabdomyolysis was 31 days and 24% of cases were fatal. Owing to the high fatality associated with this co-administration and the long duration of treatment before rhabdomyolysis occurrence, fusidic acid should be used if there is no appropriate alternative, as long as statin therapy is interrupted for the duration of fusidic acid therapy, and perhaps a week longer. Rarely will interruption of this sort have adverse consequences for the patient., (© 2018 The British Pharmacological Society.) more...

Background: In individuals with cystic fibrosis (CF), colonization with methicillin-resistant Staphylococcus aureus (MRSA) was reported to be associated with a deterioration of pulmonary disease as reflected by an accelerated decline in lung function. Thus, an early eradication of MRSA could be beneficial in these patients. Here, we report on an intensified MRSA eradication protocol., Methods: Since 2012 a protocol for the eradication of newly acquired MRSA has been used in our CF Clinic, combining oral rifampicin and fusidic acid, inhaled vancomycin, nasal mupirocin, local antiseptic treatment and hygienic directives all of which are applied for only 7 days during an inpatient hospital stay., Results: Since 2012 seven patients (3 male, 4 female; age range 4 to 30 years) newly acquired MRSA. In 6 of the 7 patients (86%) successful eradication of MRSA was achieved upon first treatment using the protocol described above. In one patient a second course of treatment was performed which, however, also failed to eliminate the colonizing MRSA., Conclusions: Our protocol led to an eradication rate of 86%. The impact of each individual component of the protocol remains to be determined. more...

Background: Hidradenitis suppurativa is a chronic inflammatory cutaneous disorder that involves the infundibular terminal follicles in areas rich in apocrine glands and associated with the formation of abscesses and fistulating sinus. The clinical course is variable, and definitive evidence-based guidelines for the management are not well-established. Conservative treatment is controversial, and surgical excision is the recommended method. Herein, we aim to analyze the results of a modified conservative tissue preserving management protocol for stage I axillary hidradenitis suppurativa., Methods: A prospective cohort study of the results of 627 patients who were diagnosed and treated for stage I axillary hidradenitis suppurativa between January 2001 and December 2010 was done. Three hundred and forty nine (55.7%) were females, and 278 (44.3%) were males. The modified conservative treatment protocol consisted of three times per day washing the affected area with antibacterial soap, application of warm compresses for 10 min, followed by application of topical sodium fusidate 2% ointment (fusidic acid), with abstinence of armpits shaving during the treatment period., Results: Four hundred and sixty one (73.5%) patients had complete healing within two weeks, 127 (20.3%) within three weeks, 39 (6.2%) within four weeks. The recurrence rate was 5.9% (37 patients) in which all patients were retreated conservatively and had complete healing, none required surgical intervention., Conclusions: We conclude that hidradenitis suppurativa continues to be a challenging disease for patients and physicians. Tissue preserving conservative method using the fusidic acid ointment for treating stage I axillary hidradenitis suppurativa showed a promising result. Further research should be conducted on the optimal treatment regimen. more...

Background: Seborrheic dermatitis (SD) is a common inflammatory skin condition. The etiology is unclear, although overgrowth of Malassezia on the skin has been suggested to cause SD. This study investigated whether colonization with Staphylococcus plays a role in facial SD, which was not well addressed previously., Methods: The study was conducted from September 1, 2011 to February 20, 2012 in the First Hospital of China Medical University. In the first phase, the study evaluated the level of transepidermal water loss (TEWL) and the number of colony-forming units (CFU) of Staphylococcus in defined skin areas of SD patients who were human immunodeficiency virus (HIV) seropositive (HIV [+] SD [+] group, n = 13), classical SD (HIV [-] SD [+] group, n = 24) patients, HIV seropositive-non-SD (HIV [+] SD [-] group, n = 16) patients, and healthy volunteers (HIV [-] SD [-] group, n = 16). In the second phase, we enrolled another cohort of HIV (-) SD (+) patients who applied topical fusidic acid (n = 15), tacrolimus (n = 16), or moisturizer (n = 12). Changes in the Seborrheic Dermatitis Area Severity Index (SDASI), TEWL, and Staphylococcus density were evaluated 2 weeks later. Comparisons of each index were performed using analysis of variance (ANOVA) and least significant difference method., Results: The level of TEWL was greater through lesional sites in the HIV (+) SD (+) group than that in HIV (+) SD (-) and HIV (-) SD (-) groups (95% confidence interval [CI]: 18.873-47.071, P < 0.001 and 95% CI: 28.755-55.936, P < 0.001, respectively). The number of CFU of Staphylococcus was greater in the HIV (+) SD (+) group than that in HIV (+) SD (-) and HIV (-) SD (-) groups (95% CI: 37.487-142.744, P = 0.001 and 95% CI: 54.936-156.400, P < 0.001, respectively). TEWL was significantly more improved in patients treated with tacrolimus and fusidic acid than that in those treated with moisturizers (95% CI: 7.560-38.987, P = 0.004 and 95% CI: 4.659-37.619, P = 0.011, respectively). Topical tacrolimus and fusidic acid were significantly associated with decreased SDASI as compared with moisturizer (95% CI: 0.03-0.432, P = 0.025 and 95% CI: 0.033-0.44, P = 0.024, respectively)., Conclusions: High colonization with Staphylococcus epidermidis, along with impaired skin permeability barrier function, contributes to the occurrence of SD. more...

Objective: Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus. It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors., Method: We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry., Results: In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection (n=28; 34.6%) followed by skin and soft tissues (n=23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI (pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus., Conclusion: This study confirms the pathogenicity of S. lugdunensis, particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.) more...

Trichomycosis is a superficial infection caused by Corynebacterium flavescens, which regularly affects axillary, and to a a lesser extent, pubic, scrotal and intergluteal, and exceptionally, head hairs or trichomycosis capitis (TC). This condition is characterised by the formation of bacterial nodules. Clinically, it can be confused with white piedra or pediculosis. The diagnosis is made by microscopic and dermoscopic observation and confirmed by culture., Objective: To present a case of TC in an infant and illustrate the microscopic, dermoscopic, and ultrastructural characteristics., Clinical Case: A 6 month-old boy, otherwise healthy, with multiple yellowish concretions on the hairs of the head. TC was confirmed by yellow fluorescence with Wood’s light; white-yellowish beads, like “rosaries of crystalline stones’’ were observed on dermoscopy, direct examination showed bacterial masses, and Corynebacterium flavescens was identified by culture. A superficial infection, without perforation of the hairs, was confirmed by electron microscopy. Treatment with fusidic acid for 3 weeks achieved a clinical and microbiological cure., Conclusion: TC is a rare condition that affects children, and tends to be mistaken for other diseases of the hair, such as pediculosis and mycotic infections. more...

Trombiculiasis represents a striking emerging infestation in humans. In fact, modified lifestyles and easy and quick traveling around the globe, together with the altered ecology and habits of the parasite Neotrombicula autumnalis, make this original epizoonosis an extraordinary example of synanthropic dermatosis. We present an additional clinical image of this unusual parasite transmission from animals to humans occurring in a trekker in Calabria, Italy. more...

Background:  Fusidic acid (FA) has been used for decades for bone infection, including prosthetic joint infection (PJI), often in combination with rifampin (RIF). An FA/RIF pharmacokinetic interaction has not previously been described., Methods:  In a phase 2 open-label randomized study, we evaluated oral FA/RIF vs standard-of-care (SOC) intravenous antibiotics for treatment of hip or knee PJI. Outcome assessment occurred at reimplantation (week 12) for subjects with 2-stage exchange, and after 3 or 6 months of treatment for subjects with hip or knee debride and retain strategies, respectively., Results:  Fourteen subjects were randomized 1:1 to FA/RIF or SOC. Pharmacokinetic profiles were obtained for 6 subjects randomized to FA/RIF. FA concentrations were lower than anticipated in all subjects during the first week of therapy, and at weeks 4 and 6, blood levels continued to decline. By week 6, FA exposures were 40%-45% lower than expected., Conclusions:  The sponsor elected to terminate this study due to a clearly illustrated drug-drug interaction between FA and RIF, which lowered FA levels to a degree that could influence subject outcomes. Optimization of FA exposure if used in combination with RIF should be a topic of future research., Clinical Trials Registration:  NCT01756924., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.) more...

Staphylococcus aureus is one of the main etiologies of bone and device-related infections. Treatment of these orthopedic infections combines mostly rifampicin with other antibiotics. The recurrence or failure rate after fusidic acid/rifampicin treatment remains low (<10%). We discuss here a case of antibiotic treatment failure for Staphylococcus aureus bone infection with in vivo selection of rifampicin and fusidic acid resistance. We also report a new mutation in fusA gene involved in fusidic acid resistance. more...

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., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.) more...

Background: People with cystic fibrosis (CF) may work in healthcare settings risking nosocomial pathogen acquisition. The aim of this study was to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in adult healthcare workers with CF (HCWcf)., Methods: Data was collected in this observational study on MRSA acquisition from 405 CF patients attending an adult CF centre in Australia between 2001-2012. Demographic and clinical characteristics were compared between HCWcf and non-HCWcf. A sub-analysis was subsequently performed to compare demographic and clinical characteristics between those patients (HCWcf versus non-HCWcf) that acquired MRSA. We also investigated rates of chronic MRSA infection and the outcome of eradication treatment in HCWcf., Results: A higher proportion of HCWcf acquired MRSA [n = 10/21] compared to non-HCWcf [n = 40/255] (P <0.001). The odds of MRSA acquisition were 8.4 (95 % CI, 3.0 - 23.4) times greater in HCWcf than non-HCWcf. HCWcf with MRSA were older (P = 0.02) and had better lung function (P = 0.009), yet hospitalisation rates were similar compared to non-HCWcf with MRSA. Chronic MRSA infection developed in 36/50 CF patients (HCWcf, n = 6; non-HCWcf, n = 30), with eradication therapy achieved in 5/6 (83 %) HCWcf., Conclusions: The rate of MRSA incidence was highest in HCWcf and the workplace is a possible source of acquisition. Vocational guidance should include the potential for MRSA acquisition for CF patients considering healthcare professions. more...

Background: Hidradenitis is a disorder where abscesses appear after the infection of the apocrine sweat glands. It is located normally in the axillae, groin, perineal region, and the scalp., Clinical Case: A 37 year old male was referred by his GP to the General Surgery Department with axillary hidradenitis which had evolved over the years. The physical examination shows signs of hidradenitis in both axillae, with a noticeable suppurative hidradenitis in the right armpit. En bloc extirpation was performed to remove the whole affected area. The pathological examination revealed a cutaneous leishmaniasis. Subsequently, fucidin was administered topically, as well as local infiltrations of one millilitre of Glucantime™., Discussion: Hidradenitis normally appears in intertriginous areas and its manifestation is accompanied by recurrent subcutaneous nodules. The incidence rate in females is three times higher than in males. The isolated Hidradenitis caused by Leishmania is a rare condition presented only in endemic areas or in immunocompromised patients, such as HIV-infected patients. Clinical manifestations can be different and the diagnosis can be confirmed through haematoxylin-eosin. The main pattern displays a disorganised granuloma without necrosis. Systemic or topical treatment can be applied. Immunotherapy treatment is the most common., Conclusions: Hidradenitis caused by Leishmania in HIV-negative patients is a rare condition. Therefore it is important to perform a good histological diagnosis and to administer the right treatment., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.) more...