Target attainment of intravenous lefamulin for treatment of acute bacterial skin and skin structure infections.

OBJECTIVES: Lefamulin is a pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). Its spectrum of activity, good penetration into soft tissues and low rates of cross-resistance also make lefamulin a potentially valuable option for treatment of acute bacterial skin and skin structure infections (ABSSSIs). A Phase 2 trial of lefamulin for ABSSSI indicated similar efficacy of 100 and 150 mg q12h IV dosing regimens. In the present study, the potential of lefamulin for this indication was further evaluated from a translational pharmacokinetic/pharmacodynamic perspective. METHODS: PTA was determined for various dosages using Monte Carlo simulations of a population pharmacokinetic model of lefamulin in ABSSSI patients and preclinical exposure targets associated with bacteriostasis and a 1-log reduction in bacterial count. Overall target attainment against MSSA and MRSA was calculated using lefamulin MIC distributions. RESULTS: Overall attainment of the bacteriostasis target was 94% against MSSA and 84% against MRSA for the IV dosage approved for CABP (150 mg q12h). Using the same target, for the 100 mg q12h regimen, overall target attainment dropped to 68% against MSSA and 50% against MRSA. Using the 1-log reduction target, overall target attainment for both regimens was <40%. CONCLUSIONS: Lefamulin at the currently approved IV dosage covers most Staphylococcus aureus isolates when targeting drug exposure associated with bacteriostasis, suggesting potential of lefamulin for the treatment of ABSSSIs. Lefamulin may not be appropriate in ABSSSI when rapid bactericidal activity is warranted.

Effective Treatment of Cutaneous Mold Infections by Antimicrobial Blue Light That Is Potentiated by Quinine.

BACKGROUND: Cutaneous mold infections commonly result from an array of traumatic injuries that involve direct inoculation of contaminated soil into wounds. Here, we explored the use of antimicrobial blue light (aBL; 405 nm wavelength) and the combination of aBL with quinine hydrochloride (aBL + Q-HCL) for the treatment of cutaneous mold infections. METHODS: Efficacy of aBL and aBL + Q-HCL in killing clinically important pathogenic molds (Aspergillus fumigatus, Aspergillus flavus, and Fusarium oxyprorum) was investigated. Ultraperformance liquid chromatography identified and quantified endogenous porphyrins in the mold conidia. Finally, a mouse model of dermabrasion wound infected with a bioluminescent variant of A. fumigatus was developed to investigate the efficacy of aBL in treating cutaneous mold infections. RESULTS: We demonstrated that mold conidia are tolerant to aBL, but Q-HCL enhances efficacy. Transmission electron microscopy revealed intracellular damage by aBL. aBL + Q-HCL resulted in intracellular and cell wall damage. Porphyrins were observed in all mold strains, with A. fumigatus having the highest concentration. aBL and aBL + Q-HCL effectively reduced the burden of A. fumigatus within an established dermabrasion infection and limited recurrence posttreatment. CONCLUSIONS: aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.

Potential Synergistic Action of Bioactive Compounds from Plant Extracts against Skin Infecting Microorganisms.

The skin is an important organ that acts as a physical barrier to the outer environment. It is rich in immune cells such as keratinocytes, Langerhans cells, mast cells, and T cells, which provide the first line of defense mechanisms against numerous pathogens by activating both the innate and adaptive response. Cutaneous immunological processes may be stimulated or suppressed by numerous plant extracts via their immunomodulatory properties. Several plants are rich in bioactive molecules; many of these exert antimicrobial, antiviral, and antifungal effects. The present study describes the impact of plant extracts on the modulation of skin immunity, and their antimicrobial effects against selected skin invaders. Plant products remain valuable counterparts to modern pharmaceuticals and may be used to alleviate numerous skin disorders, including infected wounds, herpes, and tineas.

Atopic Dermatitis: Diagnosis and Treatment.

Atopic dermatitis (atopic eczema) is a chronic relapsing and remitting inflammatory skin disease affecting one in 10 people in their lifetime. Atopic dermatitis is caused by a complex interaction of immune dysregulation, epidermal gene mutations, and environmental factors that disrupts the epidermis causing intensely pruritic skin lesions. Repeated scratching triggers a self-perpetuating itch-scratch cycle, which can have a significant impact on the patient's quality of life. The American Academy of Dermatology has created simple diagnostic criteria based on symptoms and physical examination findings. Maintenance therapy consists of liberal use of emollients and daily bathing with soap-free cleansers. Use of topical corticosteroids is the first-line treatment for atopic dermatitis flare-ups. Pimecrolimus and tacrolimus are topical calcineurin inhibitors that can be used in conjunction with topical corticosteroids as first-line treatment. Ultraviolet phototherapy is a safe and effective treatment for moderate to severe atopic dermatitis when first-line treatments are not adequate. Antistaphylococcal antibiotics are effective in treating secondary skin infections. Oral antihistamines are not recommended because they do not reduce pruritus. Evidence is lacking to support the use of integrative medicine in the treatment of atopic dermatitis. Newer medications approved by the U.S Food and Drug Administration, such as crisaborole and dupilumab, are effective in treating atopic dermatitis but are currently cost prohibitive for most patients.

Antifungal activity of Mongolian medicinal plant extracts.

The in vitro antifungal activity of extracts obtained from 14 medicinal plants of the mongolian flora were investigated by measuring their minimal inhibitory concentration (MIC) against fungi cause of cutaneous diseases such as Candida species, dermatophytes and Malassezia furfur. Among the species examined, Stellaria dichotoma L., Scutellaria scordifolia L. Aquilegia sibirica Fisch. Et Schrenk. and Hyoscyamus niger L. extracts demonstrated antifungal activity against all studied fungi. In particular, S. scordifolia L. methanol extract, obtained at room temperature, showed the best activity against Candida spp., Malassezia furfur and dermatophytes with GMMIC50 values of 22 µg/mL, 64 µg/mL and 32 µg/mL, respectively. The flavones, luteolin and apigenin, identified in S. scordifolia extracts, and rutin identified in S. dichotoma and Hyoscyamus niger L. extracts, could be responsible of the observed antifungal activity.

Case report of cutaneous nodule caused by Gordonia bronchialis in an immunocompetent patient after receiving acupuncture.

Gordonia species were recently found to cause human infection. Most Gordonia bronchialis infections are associated with sternal wounds and foreign bodies. Here, we present a case of a firm cutaneous nodule caused by G. bronchialis on an immunocompetent patient's lower extremity after receiving acupuncture. Our present case indicates that spontaneous cutaneous infection of G. bronchialis can develop even in a healthy patient. With the popularity of complementary and alternative medicine, physicians should be aware that G. bronchialis infection can be associated with Oriental medicine similar to mycobacterial infection. Recognizing the diverse clinical features of newly emerging Gordonia species will facilitate appropriate diagnosis and management of future patients.

Resistencias de los patógenos más comunes en procesos bacterianos de manejo ambulatorio y tratamiento antibiótico de elección / Resistances of the most common pathogens in bacterial processes of ambulatory management and antibiotic treatment of choice

El uso de antibióticos siempre supone un impacto sobre la flora bacteriana, patógena y colonizadora, del organismo al que se administran seleccionando el crecimiento de cepas resistentes a su acción. Y esto, la inducción de resistencias bacterianas, debe considerarse un efecto adverso de este grupo de fármacos. En España, la población pediátrica recibe más antibióticos que en otros países de Europa y hay estudios que muestran un porcentaje importante de inadecuación en los tratamientos antibióticos prescritos. Por este motivo y porque está demostrado que en poblaciones con un mayor consumo de antibióticos las tasas de resistencias microbianas son más altas, es preciso mejorar la prescripción antibiótica con el objetivo de controlar la infección, minimizando el riesgo de producir efectos adversos y de inducir resistencias. Para ello se deben confirmar las infecciones bacterianas utilizando los métodos diagnósticos disponibles y, cuando la prescripción se realice empíricamente, se debe seleccionar el antibiótico más adecuado y selectivo en función de los patógenos responsables de cada proceso, el patrón de resistencias y sensibilidad de los mismos, las características del antibiótico y del propio paciente. Es importante que estos datos sean locales, actualizados y correspondan a muestras de pacientes semejantes al paciente atendido. A continuación se describen los datos concretos a tener en cuenta para los procesos bacterianos más frecuentes de manejo ambulatorio

Use of antibiotics has always an impact on the microbiome of the person who receives the treatment, in both pathogen and saprophytic bacteria. Antibiotics cause a selection of resistant bacteria, and this fact must be considered an adverse effect. Pediatric populations in Spain receive more antibiotics than children from other European countries. Different studies show an inadequacy in an important percentage of treatments prescribed. Because of this reason, and also because of the known fact that populations with a higher consume of antibiotics develop higher resistance rates, we need to make improvements in antibiotic prescription. The goal must be to control infections while minimizing the risk of adverse effects and induction of resistances. In order to achieve this goal, bacterial infections must be confirmed with available diagnostic methods, and in empirical prescriptions, the choice of the antibiotic prescribed must be done according to the usual pathogens responsible for the process, resistance patterns, and sensitivity, characteristics of the antibiotic, and the patient. Those data must be current, collected locally, and taken from a population resembling closely the patient that will be prescribed the antibiotic treated. We are going to describe the precise data to take in account in the most usual bacterial infections, to be managed in community settings

Multi-antibiotic resistant extended-spectrum beta-lactamase producing bacteria pose a challenge to the effective treatment of wound and skin infections.

INTRODUCTION: The increasing incidence of antibiotic resistant bacteria is a concern both to the clinicians and the patients due to obvious consequences such as treatment failures, prolonged patients' stay in hospital and nosocomial infections. The choice of the first antibiotic therapy in emergency wards in hospitals is usually not based on patient-specific microbial culture and susceptibility test result.This study is aimed at profiling extended-spectrum beta-lactamase (ESBL) producing bacteria associated with wound injuries and highlighting their multi-antibiotic resistance character. METHODS: Sixty-three wound swab samples were collected and cultured on nutrient agar and on selective media. Evaluation for ESBL production was by phenotypic method while the antibiogram screening was by disc-diffusion. RESULTS: The wounds evaluated were diabetic sore (14), cancer wounds (12), surgical wounds (17), wounds due to road traffic accidents (10) and wounds from fire burn (10). The result showed that 61 wounds were infected and the prevalence of the infecting pathogens was Escherichia coli 17.46%, Klebsiella Pneumonia 14.28%, Salmonella typhi 12.79%, Pseudomonas Aeruginosa 34.92% and Staphylococcus aureus 17.46%. Thirty four (55.74 %) isolates were ESBL producers, greater than 50% of which being Pseudomonas Aeruginosa. The antibiogram study of the ESBL producers showed multi-drug resistance with resistance highest against ampicillin (100%), followed by cephalosporins: cefuroxime (94.12%) and ceftriaxone (61.76%). No resistance was recorded against the ß-lactamase inhibitors: amoxicillin/clavulanate and ceftriaxone/sulbactam. There was a high incidence (55.74 %) of ESBL-producing microbes in the wounds. The isolates were mostly multi-antibiotic resistant. CONCLUSION: Multi-drug resistant ESBL-producing bacteria are common in wound infections in the community. However, amoxicillin/clavulanate or ceftriaxone/sulbactam may be used to treat most patients with such infections in the hospital. This may guide antibiotic selection and use in trauma, most especially in resource limited countries where laboratory test is unaffordable for a majority of patients.

Low yield of blood and wound cultures in patients with skin and soft-tissue infections.

BACKGROUND: Current guidelines recommend blood cultures in skin and soft-tissue infection (SSTI) patients only with signs of systemic toxicity and wound cultures for severe purulent infections. Our objectives were to determine: 1) blood and wound culture yields in patients admitted with SSTIs; 2) whether injection drug users (IDUs) and febrile patients had higher blood culture yields; and 3) whether blood and wound cultures grew organisms sensitive to typical SSTI empiric antibiotics. METHODS: We prospectively enrolled adult patients admitted from the ED with SSTIs at an urban hospital. We recorded patient characteristics, including IDU, comorbidities and temperatures, and followed admitted patients throughout their hospital course. RESULTS: Of 734 SSTI patients enrolled, 246 (33.5%) were admitted. Of 86 (35.0%) patients who had blood cultures, six had positive cultures (yield=7.0%; 95% confidence intervals [CIs] 3.2-14.4); 4 were methicillin sensitive Staphylococcus aureus (MSSA) and 2 were methicillin resistant (MRSA). Of 29 febrile patients, 1 had a positive culture (yield=3.5%; 95% CI 0.6-17.2). Of 101 admitted IDU patients, 46 (46%) received blood cultures, and 4 had positive cultures (yield=8.7%; 95% CI 3.4-20.3). Of 89 patients with purulent wounds, 44 (49.4%) patients had ED wound cultures. Thirteen had positive cultures (yield=29.6%; 95% CI 18.2-44.2%). Most were MRSA, MSSA, and group A Streptococcus species - all sensitive to Vancomycin. CONCLUSIONS: Febrile and IDU patients had low yields of blood cultures similar to yields in non-IDU and afebrile patients. All blood and wound culture species were adequately covered by currently recommended empiric antibiotic regimens.

The potential benefits of using aloe vera in stoma patient skin care.

Individuals living with an ostomy may suffer from a variety of peri-stomal skin complications related to the use of their stoma appliance or accessories. These conditions can be serious enough to significantly impact on a patient's quality of life and may result in severe clinical complications (such as infection). This article is a review of the literature with the objective of investigating and presenting evidence for the well-documented use of aloe vera in the prevention of skin conditions similar to those seen in peri-stomal skin complications. An exploration for the potential use of aloe vera directly or indirectly (as an adjunct to medical devices such as wafers) in stoma patients is presented with the view that this use may be beneficial in the prevention of such peri-stomal skin complications.

Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review.

The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.

Ethnobotanical survey of traditionally used medicinal plants for infections of skin, gastrointestinal tract, urinary tract and the oral cavity in Borabu sub-county, Nyamira county, Kenya.

ETHNOPHARMACOLOGICAL RELEVANCE: Different communities throughout the world have specialized and profound knowledge on the use medicinal plants for various diseases. However, the detailed information on the respective use may extinct in near future as this knowledge is passed only orally among generations in most of the communities. AIM OF THE STUDY: The present survey aimed to document the use of medicinal plants by traditional healers from the Kisii community, Borabu sub-county in Nyamira county, Kenya, to treat infections of the urinary tract, oral cavity, gastrointestinal system and the skin and to evaluate the social context in which the healers work and practice. MATERIALS AND METHODS: Validated questionnaires were applied to 50 traditional healers in the study region, followed by interviews and structured conversations. Information on the relevant traditionally used medicinal plants and their use were documented, including sampling and identification of voucher specimens. RESULTS: The ethnopharmacological survey revealed 25 medicinal plant species belonging to 19 families. It got evident that most of these species will be extinct in the near future unless appropriate measures are taken, as it turned out difficult to collect some of the wild growing species. Elaeodendron buchananii Loes, Erlangea marginata S. Moore, Acacia gerrardii Benth., Balanites orbicularis Sprague, Solanum renschii Vatke and Orthosiphon hildebrandtii Vatke have not been described before for its medicinal use. Among the 25 species collected from the various regions of Borabu sub-county Urtica dioica L. was the only medicinal plant that was collected from all regions. In contrast Erythrina abyssinica and Rhus natalensis were found in only two regions of the study area. CONCLUSION: The traditional medicinal use of the reported plants for infections should be documented and a great need of awareness from scientists and local government for improved preservation or field cultivation of some species is obvious.

Chinese herbal medicines for treating skin and soft-tissue infections.

BACKGROUND: Skin and soft-tissue infections (SSTIs) are common infections of the epidermis, dermis or subcutaneous tissue. SSTIs range in severity from minor, self-limiting, superficial infections to deep, aggressive, gangrenous, life-threatening infections. Some classifications divide SSTIs into 'complicated' and 'uncomplicated' infections based on clinical severity. Treatments of SSTIs involves antibiotic therapy, surgical debridement or drainage, and resuscitation if required. Sometimes these treatments are limited by high treatment costs, bacterial resistance to antibiotics and side effects, therefore, many people with SSTIs are turning to Chinese herbal medicines to treat this problem.Chinese herbal medicines are natural substances that have been used for centuries in China where they are generally considered to be effective for SSTIs. Some Chinese herbal medicines have been shown to have antibacterial and anti-inflammatory properties, although a few herbal medicines have been reported to have side effects. Therefore there is a need to review the current clinical evidence systematically to inform current practice and guide future studies on Chinese herbal medicines for SSTIs. OBJECTIVES: To evaluate the benefits and harms of Chinese herbal medicines for treating skin and soft-tissue infections (SSTIs). SEARCH METHODS: Searches were not restricted by date, language or publication status. In July 2014 we searched the following electronic databases: the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; Ovid AMED (Allied and Complementary Medicine); and EBSCO CINAHL. SELECTION CRITERIA: All randomised controlled trials (RCTs) in people with SSTIs that compared Chinese herbal medicines with another intervention or control. DATA COLLECTION AND ANALYSIS: Two review authors screened the literature search results independently; there were no disagreements. MAIN RESULTS: We identified no RCTs that met the inclusion criteria. AUTHORS' CONCLUSIONS: There is currently no information available from RCTs to support or refute the use of Chinese herbal medicines in treating people with SSTIs.

Physicochemical characteristics, nutritional properties, and health benefits of argan oil: a review.

The argan tree (Argania spinosa L. Skeels), an endemic tree in Morocco, is the most remarkable species in North Africa, due to its botanical and bioecologic interest as well as its social value. Argan oil is traditionally well known for its cardioprotective properties and it is also used in the treatment of skin infections. This paper gives an overview of scientific literature available on nutritional and pharmacologic properties of argan oil. Owing to its unique organoleptic properties associated with its cardioprotective properties, argan oil has found, recently, its place in the highly competitive international edible oil market. This success is a very positive sign for the preservation of the argan tree, the argan forests and, therefore, in general, the biodiversity.

[Dynamics of local expression of connexin-43 and basic fibroblast growth factor receptors in patients with skin and soft-tissue infections against the background of diabetes mellitus type II].

Clinical results of wound healing dynamics were studied in 60 patients with soft-tissue infection against the background of diabetes mellitus type II. At the same time the study considered indices of intercellular contacts protein tissue expression such as connexin 43 (Cx43) and basic fibroblast growth factor receptors (bFGFR). The basic therapy of biopsy material of wound borders was applied. The reduction of bFGFR expression and the minor growth of Cx43 expression were observed. The pain syndrome proceeded for a long time and there were signs of perifocal inflammation, retard wound healing with granulation tissue. The application of combined method of ozone therapy which included autohemotherapy with ozone and an external management of wound by ozone-oxygen mixture facilitated to considerable shortening of inflammatory phase and regeneration. It was associated with increased Cx43 expression (in 1.9 times) in comparison with initial level and bFGFR was enlarged in 1.7 times to eighth day of postoperative period.

La terapia fotodinámica con metilaminolevulinato puede ser útil en el manejo de las infecciones por Scytalidium / Photodynamic Therapy With Methyl-aminolevulinate can be Useful in the Management of Scytalidium Infections

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Fish tank granuloma caused by Mycobacterium marinum.

INTRODUCTION: Mycobacterium marinum causes skin and soft tissue, bone and joint, and rare disseminated infections. In this study, we aimed to investigate the relationship between treatment outcome and antimicrobial susceptibility patterns. A total of 27 patients with M. marinum infections were enrolled. METHODS: Data on clinical characteristics and therapeutic methods were collected and analyzed. We also determined the minimum inhibitory concentrations of 7 antibiotics against 30 isolates from these patients. RESULTS: Twenty-seven patients received antimycobacterial agents with or without surgical debridement. Eighteen patients were cured, 8 failed to respond to treatment, and one was lost to follow-up. The duration of clarithromycin (147 vs. 28; p = 0.0297), and rifampicin (201 vs. 91; p = 0.0266) treatment in the cured patients was longer than that in the others. Surgical debridement was performed in 10 out of the 18 cured patients, and in 1 of another group (p = 0.0417). All the 30 isolates were susceptible to clarithromycin, amikacin, and linezolid; 29 (96.7%) were susceptible to ethambutol; 28 (93.3%) were susceptible to sulfamethoxazole; and 26 (86.7%) were susceptible to rifampicin. However, only 1 (3.3%) isolate was susceptible to doxycycline. DISCUSSION: Early diagnosis of the infection and appropriate antimicrobial therapy with surgical debridement are the mainstays of successful treatment. Clarithromycin and rifampin are supposed to be more effective agents.

Telavancin pharmacokinetics and pharmacodynamics in patients with complicated skin and skin structure infections and various degrees of renal function.

This study characterized the pharmacokinetic/pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved telavancin renal dose adjustment schemes. A previously published two-compartment open model with first-order elimination and a combined additive and proportional residual error model derived from 749 adult subjects in 11 clinical trials was used to simulate the individual concentration-time profiles for 10,260 subjects (NONMEM). The dosing regimens simulated were 10 mg/kg of body weight once daily for individuals with creatinine clearances (CL(CR)s) of >50 ml/min, 7.5 mg/kg once daily for individuals with CL(CR)s of 30 to 50 ml/min, and 10 mg/kg every 2 days for those with CL(CR)s of <30 ml/min. The area under the concentration-time curve (AUC) under one dosing interval (AUC(τ)) was computed as dose/CL. The probability of achieving an AUC(τ)/MIC ratio of ≥ 219 was evaluated separately for each renal dosing scheme. Evaluation of the dosing regimens demonstrated similar AUC values across the different renal function groups. For all renal dosing strata, >90% of the simulated subjects achieved an AUC(τ)/MIC ratio of ≥ 219 for MIC values as high as 2 mg/liter. For patients with CL(CR)s of <30 ml/min, the probability of target attainment (PTA) exceeded 90% for both the AUC0₋24 (AUC from 0 to 24 h) and AUC24₋48 intervals for MICs of ≤ 1 mg/liter. At a MIC of 2 mg/liter, the PTAs were 89.3% and 23.6% for the AUC0₋24 and AUC24₋48 intervals, respectively. The comparable PTA profiles for the three dosing regimens across their respective dosing intervals indicate that the dose adjustments employed in phase III trials for complicated skin and skin structure infections were appropriate.

Coenzyme Q(10), vitamin E, selenium, and methionine in the treatment of chronic recurrent viral mucocutaneous infections.

OBJECTIVE: Host defense and latency determinants in viral recurrent dermatologic infections are not entirely understood, as conventional protocols are inadequate to achieve fast healing and relapse prevention. Endogenously produced oxygen/nitrogen reactive species (ROS/RNS) are essential for antiviral immune defense, while their excess may aggravate skin inflammation. Here, we sought a nutritional approach capable of controlling ROS/RNS balance to accelerate recovery and inhibit recurrences of two mucocutaneous chronic DNA-virus infections. METHODS: Two controlled clinical trials evaluated the feasibility of ROS/RNS-modulating nutriceutical dosages of coenzyme Q(10), RRR-α-tocopherol, selenium aspartate, and L-methionine associated with established therapies. Clinical trial 1 evaluated 68 patients with relapsing human papillomavirus skin warts treated with cryotherapy followed by 180 d of nutriceutical/placebo administration. Clinical trial 2 compared the combination of acyclovir followed by 90 d of nutriceutical administration versus acyclovir alone in patients with recurrences of herpes simplex genitalis (n = 60) or herpes zoster (n = 29). Viral DNA levels were assessed by polymer chain reaction, biomarkers of antiviral defense (peroxynitrite and IFNα/γ) and antioxidant capacity (lipophilic antioxidants and glutathione) were assayed by biochemical/enzyme-linked immunosorbent assay techniques in blood fractions. RESULTS: In both trials, the nutriceutical induced significantly faster healing (P < 0.01-0.05) with reduced incidence of relapses (P < 0.05) as compared to control groups, which was confirmed by decreased viral load and increased antiviral cytokine and peroxynitrite plasma levels. Plasma antioxidant capacity was higher (P < 0.01) in the experimental versus control groups. CONCLUSIONS: Results document positive clinical outcomes of the selected nutriceutical associated with conventional protocols in the management of relapsing mucocutaneous human papillomavirus and herpes infections.