Bacteriophage therapy reduces Staphylococcus aureus in a porcine and human ex vivo burn wound infection model.

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.

A Nanocomposite Dynamic Covalent Cross-Linked Hydrogel Loaded with Fusidic Acid for Treating Antibiotic-Resistant Infected Wounds.

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.

The origin of sequence type 72 community-associated methicillin-resistant Staphylococcus aureus (MRSA) and fusidic acid (FA) resistant sequence type 5 MRSA: Analysis of FA resistance and spa type in a single center in South Korea.

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.

Neutrophil-targeted combinatorial nanosystems for suppressing bacteremia-associated hyperinflammation and MRSA infection to improve survival rates.

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.

Synthesis and structure-activity relationship studies of fusidic acid derivatives as anti-inflammatory agents for acute lung injury.

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 (IC50 = 5.382 ± 0.655 µM), IL-6 (IC50 = 7.767 ± 0.871 µM), and TNF-α (IC50 = 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.

Prevalence and genetic characteristics of fusidic acid resistant Staphylococcus aureus clinical isolates: Emergence of t030 strains carrying fusB in Tehran, Iran.

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.

Fusidic Acid and Its Major Active Metabolite Penetration into Cerebrospinal Fluid for Assessing Treatment of Intracranial Infections.

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.

Discovery of fusidic acid derivatives as novel STING inhibitors for treatment of sepsis.

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 IC50 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.

Comparative study of multidrug-resistant bacterial infections in hospitals and community settings in the region of Monastir - Tunisia.

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.

[Susceptibility of drug-resistant staphylococci isolated from different parts of the ocular anterior segment to common ophthalmic antibiotics].

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 ß-lactamase-producing (ß-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 ß-Lac and 2 ß-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 ß-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of ß-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 ß-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 (χ2=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 (χ2=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 (χ2=33.080, P<0.001). Among the 30 ß-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 (χ2=28.280, P<0.001). The sensitivity rates of five antibiotics against ß-Lac isolates from the anterior segment were both statistically significant differences (χ2=50.971, 24.543, 48.147, 44.899, 18.676; all P<0.001). The susceptibility rates of ß-Lac isolates against five antibiotics was statistically significant differences (χ2=23.383, P<0.001). The sensitivity of cefazolin sodium and fusidic acid against ß-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 ß-Lac-producing drug-resistant Staphylococcus infection.

Fusidic acid in a tertiary hospital: an observational study focusing on prescriptions, tolerance and susceptibility of Staphylococcus and Cutibacterium spp. strains from bone samples.

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.

Efficacy of 5% permethrin-2% fusidic acid cream compared to 5% permethrin-placebo in the treatment of impetiginized scabies.

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.

Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system.

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.

Not a wild goose chase: long-lasting MRSA negative status following eradication therapy for chronic MRSA infection in patients with cystic fibrosis.

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.

An unusual outbreak in the Netherlands: community-onset impetigo caused by a meticillin-resistant Staphylococcus aureus with additional resistance to fusidic acid, June 2018 to January 2020.

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.

Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage among patients with diabetes at the Korle Bu Teaching Hospital.

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.

Scleredema adultorum of Buschke associated with hypothyroidism and liver cirrhosis.

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.

Do Antimicrobial Resistance Patterns Matter? An Algorithm for the Treatment of Patients With Impetigo.

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.