Management of acute bacterial skin and skin structure infections in India: are we equipped to meet the challenges of the growing menace of methicillin-resistant Staphylococcus aureus?

Staphylococcus aureus (S. aureus) is a Gram-positive facultative anaerobic bacterium that colonizes the skin and nasal passages of humans. The incidence of invasive S. aureus infections has increased over the past decades and is associated with poor outcomes and high mortality rates. S. aureus is responsible for almost one-third of acute bacterial skin and skin structure infections with methicillin-resistant Staphylococcus aureus (MRSA) accounting for a large proportion of these. The S. aureus strains prevalent inIndia are more aggressive and there are recent reports of the emergence of the more virulent multidrug resistant lineages ST2371 and ST8. Management of these infections is complicated by the fact that antimicrobial stewardship is non-existent, the choice of treatment is often empirical and available treatment options are limited due to a high prevalence of resistance strains. Currently available anti-MRSA agents include vancomycin, teicoplanin, linezolid, daptomycin, tigecycline, and clindamycin. However, the emergence of resistant strains and several undesirable features related to the safety and tolerability of these agents have limited the options available for the management of MRSA infections. A newer, safe and efficacious antibiotic is thus an unmet need for the management of MRSA in patients with acute bacterial skin and skin structure infections. In this review we explore the current and future trends in the management of acute bacterial skin and skin structure infections highlighting the challenges in their management in India, and current progress in the development of some novel drugs for the management of MRSA infections.

Cross-sectional, Observational Study to Assess Clinical Role of Oral and Injectable Linezolid in Post-operative Diabetic Foot Ulcers: COOLD Study

Background: Diabetic foot ulcers (DFUs) remain difficult to treat with likely incriminating risk factors involving Methicillinresistant Staphylococcus aureus (MRSA). Linezolid offers complimentary consistent action against MSSA and MRSApathogens making it an ideal choice for inpatient, switch or outpatient therapy for complicated skin and skin structureinfections.Objective: The objective of the study was to compare the efficacy of injectable versus oral linezolid in the management ofpost-operative DFUs.Materials and Methods: Retrospective analyses of 100 cases receiving oral or injectable linezolid. A total of 100 subjectswere enrolled in this study. Two groups were made of 50 patients each and labeled as Group A and Group B. In Group A,tablet linezolid was given in a dose of 600 mg BD for 7 days. In Group B, injectable linezolid was given in a dose of 600 mgintravenous (IV) BD for 7 days. Clinical and bacteriological improvement was documented. In both groups tablet cefuroxime,500 mg BD was given for 7 days in conjunction with linezolid.Results: We found 90–100% improvement in wound infections and in culture reports. Results in both the groups receivingoral or IV linezolid for post-operative DFU healing were comparable when administered for 7 days. Linezolid offered hightherapeutic success rates (75–100%) against the incriminated pathogens of S. aureus with little action against Acinetobacteror Pseudomonas aeruginosa.Conclusion: These results suggest that linezolid given empirically is highly effective in the treatment of DFUs. The equivocalclinical and microbiological eradication rates for oral and injectable formulations with 7 days therapy makes them less liable forresistance induction or development.

Delafloxacin, a New Miracle in Antibiotics Armamentarium for Bacterial Infections

The persistent antibiotics resistant issue has emerged as an influencing factor to deteriorate community health. So, new antibiotics development is urgent for the treatment of bacterial infections. Alternatively, delafloxacin is an eminent new fluoroquinolone, and chemically distinct from older fluoroquinolones. There is lack of proton substituent that indicates the poor acidic property of the drug. It also has a good intracellular penetration capacity that increases the intensity of the bactericidal property in acidic environment. Delafloxacin is a super active drug against the skin and soft tissue infections (SSTIs) and community-acquired respiratory tract infections. Delafloxacin also exhibits better efficacy against pathogens which are resistant to other fluoroquinolones, such as methicillin-resistant Staphylococcus aureus (MRSA). Delafloxacin received approval from the US Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSI). Phase III clinical trial among patients with community-acquired pneumonia (CAP) is ongoing to evaluate the effectiveness of delafloxacin. From the aforementioned arguments, delafloxacin will be a prominent candidate for the upcoming antibacterial agent. Similarly, delafloxacin can be a crucial drug to fight against ABSSI.

A comparison of 20-MHz and 50-MHz ultrasonography in imaging and measuring the skin / 中华皮肤科杂志

Objective To investigate imaging characteristics of human skin in different sites by using 20-MHz and 50-MHz high-frequency ultrasonography,and to compare the reliability of skin thickness measurement by the above two approaches of ultrasonography.Methods A total of 39 healthy volunteers aged 18-39 years were enrolled into this study.Then,20-MHz and 50-MHz ultrasonography were separately performed to image 20 different sites on the body,and the thickness of the epidermis and dermis were measured and evaluated by 3 dermatologists independently.The ultrasonic images were analyzed,and the intraclass correlation coefficient (ICC) was used to assess and compare the reliability of skin thickness measurement by 20-MHz and 50-MHz ultrasound.Results The ICC values were less than or close to 0.7 in epidermal thickness measurement at almost all the tested sites between 20-MHz and 50-MHz ultrasonography,suggesting poor reliability.However,20-MHz and 50-MHz ultrasonography showed excellent reliability in dermal thickness measurement with the ICC greater than 0.75 at almost all the tested smooth and flat body sites.The 20-MHz ultrasound could provide clear images of the dermis and subcutaneous tissue,while 50-MHz ultrasound could only provide clearer images of the dermis in details.In some uneven sites with complex anatomical structures,20-MHz and 50-MHz ultrasound probes had their own advantages and disadvantages in imaging depth and detail resolution.Conclusions The 20-MHz and 50-MHz ultrasono-graphy both can serve as non-invasive imaging techniques to show structures of the epidermis and dermis better.In different parts of human body,ultrasound frequencies should be selected according to their imaging characteristics.

Use of garenoxacin: a new generation antibiotic for surgical infections.

Background: The management of skin and skin structure infections (SSSI) still continues to be global challenge. USFDA has given strong recommendation for adequate empirical antibiotic coverage to avoid further complication of the wounds. Wound complications, especially in the diabetic population, patients with low immunity remains a big challenge though other factors like site of the wound, age of the patients also play an important role. Methods: A retrospective observational study was conducted to analyze clinical utility of garenoxacin for surgical prophylaxis. A total of 100 patients, 30 patients with diabetic foot and 70 patients with post-surgical intraabdominal wounds who were prescribed garenoxacin 2×200 mg as stat dose prophylactically. Swab culture from the wound slough and drain tube samples were sent for culture/sensitivity on day 0, day 5, and day 7. Wound healing was evaluated by estimating slough discharge, size of the wound, vascularity, and overall healing. They were categorized as treatment failure group, when sough/drain-discharge reduction was ≤50%, improved if sough/drain-discharge reduction was 50-75% and cure when sough/drain-discharge reduction was 75-100%. Results: The healthy granulation tissue was observed post 7 days therapy of garenoxacin 2×200 mg in diabetic foot ulcer (DFU) patients when administered empirically before surgical debridement. In patients with post-operative infectious intraabdominal wounds, the most common isolated organisms were Enterococcus, Acinetobacter and Klebsiella. Post garenoxacin therapy used as switch therapy empirically for 5 days resulted in 100% sterile culture. While evaluating slough/draindischarge in DFU patients, 84% patients showed cure and 16% showed improvement at the end of day 7 and in patients with post-operative infectious intra-abdominal wounds cure was observed in 86% patients showed cure and 14% patient showed improvement. No side effects were reported during the study. Conclusions: Administration of garenoxacin used as empirical therapy for surgical prophylaxis and as switch therapy in patients with DFU s and post-surgical infectious wounds for the period of 5-7 days has been found effective indicating its wide spectrum of action.

Effects of vitamin C on UV-induced photoaged skin in rats / 中国比较医学杂志

Objective To study the protective effect of vitamin C on UV-induced photoaged skin structure in rats and provide a basis for clinical medicine and health care.Methods Photoaging skin models were set up by chronic ultraviolet radiation in 24 SPF female Sprague-Dawley rats, irradiated twice weekly for 4 weeks.The rat photoaged skin was induced by exposure to a total dose of 123 J/cm2 UVA and 5 J/cm2 UVB for 4 weeks.Vitamin C was administered by gastric gavage in a dose of 50 mg/kg once daily for 30 days during the model development.We compared the pathological changes in the irradiated skin using HE, Masson’ s trichrome and Victoria blue B staining, and compared the ultrastructural changes by electron microscopy.Results Rat models with photoaged skin were developed successfully.The vitamin C group showed significant reduction of pathological severity including erythema, ulcers, epidermal cell proliferation, epidermal thickness, dermis vasodilation, inflammatory cell infiltration, fibroblast proliferation, endoplasmic reticulum dilatation, mitochondrial swelling and vacuolization, elastic fibers degeneration and focal accumulation, collagen fibers swelling with uneven thickness,compared with the rats of model group at the irradiation site.Conclusions Vitamin C is effective in reducing the structural damage of UV-induced photoaged skin in rats.

Histochemistry and functional organization of the dorsal skin of Ancistrus dolichopterus (Siluriformes: Loricariidae)

The structural organization and histo-cytochemical features of dorsal skin of Ancistrus dolichopterus (acari bodo) are the main focus of this work. The epidermis, dermis and subcutis are the principal layers of the skin. The epidermis mainly consists of epithelial and mucous cells. Interspersed between them are lymphocytes, pigment cells, eosinophilic granular cells (EGC), and the taste buds as sensory structures. The high number of EGCs is implicated in general and specific immunological defense from pathogenic bacteria and multicellular parasites. The epithelial cells and mucous cells contain glycoproteins with oxidizable vicinal diols, carboxyl groups and O-sulphate esters and their high secretory activity is correlated with the bottom dwelling habit of this species. A thick stratum laxum contains overlapping osteoderms bearing denticles, and the stratum compactum make the integument thicker to help the fish in negative buoyancy for maneuvering near the bottom and protection. The entire body surface is covered by conical, backwardly directed denticles. These are composed of a dentine cone, surrounding a pulp cavity with the top covered by mineralized cap, and are the true homologues of teeth. These structures provide effective protection from abrasion and enemies. These structural peculiarities and histochemical features indicate additional physiological role of the skin of A. dolichopterus.

A organização estrutural e aspectos histo-citiquímicos da pele dorsal de Ancistrus dolichopterus (acari-bodó) são os principais alvos do presente estudo. A epiderme, a derme e a hipoderme são as principais camadas da pele. A epiderme consiste principalmente de células epiteliais e mucosas. Intercalados entre elas estão os linfócitos, as células pigmentares, as células granulares eosinofílicas (CGE), e as papilas gustativas como estruturas sensoriais. Um grande número de CGEs está relacionado em geral com a defesa imunológica específica de bactérias patogênicas e parasitas multicelulares. As células epiteliais e as células mucosas contem glicoproteínas com grupos diol oxidáveis, grupos carboxilas e ésteres O-sulfatados sendo que sua alta atividade secretória está correlacionada com o comportamento bentônico, de fundo, dessa espécie. Um espesso stratum laxum contém osteodermos sobrepostos, parecidos com dentículos, e o stratum compactum que torna o tegumento mais espesso, contribuindo com a flutuação negativa necessária ao movimento perto do fundo e proteção. Toda a superfície do corpo é coberta por dentículos cônicos retrodirecionados. Esses dentículos são compostos por um cone de dentina, envolvendo uma cavidade pulpar e com o ápice coberto por uma capa mineralizada, verdadeiros homólogos dos dentes. Essas estruturas oferecem efetiva proteção contra abrasão e oponentes. Essas peculiaridades estruturais e aspectos histoquímicos sugerem a existência de uma função fisiológica adicional para a pele de A. dolichopterus.

Tigeciclina versus vancomycin más aztreonam en el tratamiento de infecciones complicadas de piel y tejidos blandos: Experiencia en Latinoamérica / Tigecycline as effective as vancomycin plus aztreonam in the treatment of complicated skin and skin structure infections: Experience in Latin America

BACKGROUND: Treating complicated skin and skin structure infections (cSSSIs) can be challenging. Tigecycline was compared to vancomycin/aztreonam in patients with cSSSIs in a multinational trial; this article reports on the Latin American (LA) population. METHODS: Patients were randomly assigned to receive tigecycline or vancomycin/ aztreonam. Primary endpoint was clinical cure rate at test-of-cure (TOC). Several secondary endpoints and safety were also assessed. RESULTS: A subtotal of 167 LA patients from the multinational trial (N = 573) received ≥ 1 dose of study drug. At TOC, cure rates were similar between tigecycline and vancomycin/aztreonam in the clinically evaluable population.) Noninferiority of tigecycline could not be demonstrated (insufficient sample sizes). Tigecycline-treated patients had higher incidences of nausea, vomiting, anorexia; vancomycin/aztreonam-treated patients had higher incidences of pruritus and rash. CONCLUSIONS: Efficacy results in the LA population were consistent with the multinational study suggesting that tigecycline is noninferior to vancomycin/aztreonam in treating patients with cSSSI.

INTRODUCCIÓN: El tratamiento de infecciones complicadas de piel y tejidos blandos (ICPTB) puede representar un desafío. Se comparó la eficacia de tigeciclina versus vancomicina/aztreonam en pacientes con ICPTB en un estudio multicéntrico; este artículo se refiere a la experiencia en Latinoamérica (LA). MÉTODO: Se asignaron, en forma randomizada, los pacientes a dos grupos de tratamiento: tigeciclina o vancomicina/aztreonam. La meta a evaluar (outcome) primaria fue la curación clínica, denominada test de curación (TC). Se establecieron, además, metas secundarias y la evaluación de seguridad del fármaco. RESULTADOS: Un subtotal de 167 pacientes procedentes de LA, de un estudio multinacional que incluyó 573 pacientes, recibieron ≥ 1 dosis del fármaco en estudio. Al TC, los porcentajes de curación fueron similares entre tigeciclina y vanco-micina/aztreonam en los pacientes clínicamente evaluables). La no inferioridad de tigeciclina no pudo ser demostrada (tamaño de muestra insuficiente). Los pacientes tratados con tigeciclina tuvieron mayor incidencia de náuseas, vómitos y anorexia; los pacientes que recibieron vancomicina/aztreonam tuvieron mayor incidencia de prurito y rash. CONCLUSIONES: Los resultados de eficacia en LA fueron consistentes con el estudio multinacional sugiriendo que tigeciclina no es inferior a vancomicina/aztreonam en el tratamiento de pacientes con ICPTB.