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Julian J Goodman, Stanley I MartinDivision of Infectious Diseases, The Ohio State University, Columbus, OH, USAAbstract: Ceftaroline is a novel broad-spectrum cephalosporin ß-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as multidrug-resistant Streptococcus pneumoniae among other routine Gram positive and Gram negative organisms. It has been approved by the US Food and Drug Administration for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections (ABSSSIs). Ceftaroline is approved for treatment of ABSSSI due to MRSA, however currently there are no data for pneumonia due to MRSA in humans. Herein we review the major clinical trials as well as ceftaroline microbiology, pharmacokinetics, and safety, followed by a look at further directions for investigation of this new agent.Keywords: ceftaroline, pneumonia, skin infection

Purpose: The current study was performed to evaluate the effects of teaching surgical residents on the margin status after lumpectomy., Methods: A retrospective review of all patients from July 2006 to Nov 2009 was performed. The impact of the technical ability of surgical residents to perform lumpectomy was evaluated to determine if there was an effect on the margin status. A logistic regression analysis was performed to adjust for clinical variables known to affect the margin status., Results: Of 106 patients, 19% had positive margins. Residents with unsatisfactory technical skills had a positive margin rate of 34% compared to 8% for residents with satisfactory skills (p = 0.004). In the multivariate logistic regression analysis, the operating surgeon remained significantly associated with a positive margin status. Operations performed by residents with satisfactory technical skills or by attending surgeons were less likely to have positive margins than those performed by residents with unsatisfactory technical skills (OR 0.26, 95% CI 0.08-0.86; p = 0.03). After a mean follow-up of 60 months, the breast cancer-specific survival rate was 94%, and there were no local recurrences as a first event., Conclusions: The technical ability of residents may affect the margin status after lumpectomy. The importance of teaching surgical residents needs to be considered in future quality of care evaluations.

Background: Secukinumab, an anti-interleukin-17A monoclonal antibody, has demonstrated rapid and sustained efficacy in phase 3 psoriasis trials., Objectives: To examine whether partial responders could achieve improved responses with intravenous (IV) secukinumab vs. the same or a higher subcutaneous (SC) dose., Methods: Forty-three participants with moderate-to-severe psoriasis and partial response [Psoriasis Area and Severity Index (PASI) score improvement of ≥ 50% but < 75%] after 12 weeks of 300 or 150 mg SC secukinumab therapy were randomized 1 : 1 to secukinumab 10 mg kg(-1) IV (baseline, weeks 2 and 4, respectively) or secukinumab 300 mg SC (baseline, week 4). All participants subsequently received secukinumab 300 mg SC every 4 weeks (weeks 8-36). Co-primary end points were PASI 75 and Investigator's Global Assessment [2011 modified version (IGA mod 2011)] 0/1 response rates at week 8 (IV vs. SC)., Results: Higher IGA mod 2011 0/1 response rates (66.7% vs. 33.3%; P = 0.03) and a trend towards higher PASI 75 response rates (90.5% vs. 66.7%; P = 0.06) were observed with secukinumab IV vs. SC at week 8. The primary objective was not met, as the difference was not significant for both co-primary end points. Improved responses in both groups were maintained at week 40 in most participants. Safety profiles for IV and SC secukinumab were similar. The trial was underpowered owing to its small sample size., Conclusions: Improved response may be attained in patients with psoriasis achieving partial response after 12 weeks of SC secukinumab treatment by continued dosing with 300 mg SC or treatment with higher doses., (© 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Hydrocolloid technology has been proven effective in treating dermal wounds. A previous study showed that a newly developed thin hydrocolloid patch [Compeed cold sore patch (CSP)] provided multiple wound-healing benefits across all stages of a herpes simplex labialis (HSL) outbreak., Methods: An assessment of CSP efficacy and safety was conducted in an international, multicentre, assessor-blinded study, which enrolled 728 subjects with a history of recurrent HSL. Of these, 351 experienced an HSL outbreak and were randomized to use CSP (n = 179) or acyclovir cream 5% (n = 172) at the onset of symptoms until the lesion healed, for a maximum of 10 days. The primary end point was the subject's global assessment of therapy (SGAT; 0-10 scale; 0 = no response, 10 = excellent response). Multiple secondary end points included clinician-assessed healing time and subject assessment of lesion protection, noticeability and social embarrassment., Results: CSP and acyclovir were highly effective (mean SGAT = 7.89 and 8.00, respectively), with no significant difference observed (P = 0.65). The difference in healing times between products was not significant (median, 7.57 days with CSP vs. 7.03 days with acyclovir, P = 0.37). Both treatments were well tolerated., Conclusion: CSP using hydrocolloid technology provides an efficacious and safe alternative to topical antivirals in treating HSL as a wound while affording additional immediate benefits of wound protection, discretion and relief of social embarrassment.

Background: Head lice infestations are a major nuisance in school-aged children and are a worldwide public health problem. There are growing concerns about the effectiveness of current treatments owing to increasing resistance, safety, and patient noncompliance. A safe, easy to use, effective alternative is needed., Objective: A pediculicide rinse, 50% isopropyl myristate (IPM), was assessed in two phase 2 trials conducted in North America. The first trial was a nonrandomized (proof of concept) trial without a comparator conducted in Winnipeg, Canada. The second trial, conducted in the United States, was an evaluator-blinded, randomized superiority trial comparing 50% IPM rinse with a positive control (RID; pyrethrin 0.33%, piperonyl butoxide 4%). The primary end points were to determine the safety and efficacy of 50% IPM as a pediculicide rinse., Methods: Subjects meeting inclusion criteria were enrolled in the above-mentioned trials with efficacy end points 7 and 14 days post-treatment. Subjects were also evaluated on days 0, 7, 14, and 21 for the presence of erythema and edema using the Modified Draize Scale. Other comments associated with the safety evaluation (ie, pruritus) were collected., Results: IPM was found to be effective in the proof of concept study and comparator trial using a positive control. IPM was also well tolerated, with minimal adverse events. All adverse events were mild, resolving by completion of the study., Conclusion: Data suggest that IPM is a safe and effective therapy for the treatment of head lice in children and adults. IPM's mechanical mechanism of action makes development of lice resistance unlikely.

Objective: To characterize the pharmacokinetics of tacrolimus after topical application in adult and pediatric patients with moderate to severe atopic dermatitis from all clinical trials in which tacrolimus blood levels were obtained., Methods: Tacrolimus ointment 0.03% or 0.1% was applied twice daily. In the adult and pediatric pharmacokinetic studies, serial blood samples were obtained after single and repeated topical application. During the 12 clinical efficacy trials of tacrolimus ointment, single blood samples were obtained at various times relative to tacrolimus ointment application., Results: In the pharmacokinetic studies, 89% to 95% of tacrolimus whole blood concentration samples were less than 1 ng/mL; mean maximum concentrations ranged from 0.2 to 1.6 ng/mL and mean area under the blood concentration-time curves (0-12 hours) ranged from 1.4 to 13.1 ng x hr/mL. Likewise, in the clinical efficacy trials, the majority (85%-99%) of tacrolimus concentration samples were less than 1 ng/mL., Conclusions: Tacrolimus ointment is associated with minimal systemic absorption and no evidence of systemic accumulation in patients with moderate to severe atopic dermatitis and extensive disease.

Objective: To determine the safety and efficacy of photodynamic therapy (PDT) using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter "ALA") and visible blue light for the treatment of multiple actinic keratoses of the face and scalp., Design: Randomized, placebo-controlled, uneven parallel-group study., Interventions: Patients (N = 243) were randomized to receive vehicle or ALA followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1, 4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re-treated., Main Outcome Measure: Clinical response based on lesion clearing by week 8., Results: Most patients in both groups had 4 to 7 lesions. Complete response rates for patients with 75% or more of the treated lesions clearing at weeks 8 and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and 18% (10/55) and 13% (7/52), respectively, for the vehicle group (P<.001, Cochran-Mantel-Haenszel general association test). The 95% confidence interval for the difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3% to 86.3%. The week 12 response rate includes 30% of patients who received a second treatment. Most patients experienced erythema and edema at the treated sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging or burning during light treatment, which decreased or resolved by 24 hours after light treatment., Conclusion: Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp.

Objective: The purpose of this study was to further define the therapeutic value of penciclovir cream in the treatment of sunlight-induced herpes labialis by comparing its efficacy and tolerability with those of an inactive control (purified water)., Methods: In this randomized, double-blind, placebo-controlled, parallel-group clinical trial, lesions were induced by exposure to sunlight. Treatment was self-initiated within 1 hour of development of the signs or symptoms of a recurrence., Results: Healthy male and female patients (mean age, 38.3 years; range, 18 to 81 years) who had a history of sunlight-induced herpes labialis (mean of 6 recurrences in previous 12 months) applied either penciclovir cream (n = 266) or purified water (n = 275). Penciclovir cream significantly decreased the time to lesion healing (P < 0.001), with a reduction in median time of up to 2 days. The efficacy of penciclovir cream was further supported by a significant reduction in maximum lesion area (P = 0.008), a faster loss of lesion-associated symptoms (P = 0.026), and significant reductions in daily assessments of pain (P < or = 0.040), itching (P < or = 0.032), burning (P < or = 0.028), and tenderness (P < or = 0.026) as moderate or severe. These effects were reinforced by the results of the daily self-assessment of lesion attributes, with significantly fewer severe/extreme assessments of lesion size (P < or = 0.003), noticeability (P < or = 0.003), amount of scab/crust (P < or = 0.003), raised/ swollen area (P < or = 0.040), soreness/tenderness (P < or = 0.043), and overall severity (P < or = 0.001) throughout the study period., Conclusions: Penciclovir cream has demonstrated efficacy for a broad range of clinically important outcomes. Significant effects on lesion area, lesion symptoms, and other lesion attributes extend the clinical efficacy of penciclovir cream beyond lesion healing.

A high prevalence of antibodies to the hepatitis C virus (anti-HCV) has been demonstrated among patients with alcoholic liver disease, whereas the prevalence of HCV viremia in these patients remains uncertain. The aims of this study were to determine the prevalence of anti-HCV in alcoholic patients both with and without clinically apparent liver disease and to determine the presence of HCV RNA in those patients who tested positive for anti-HCV by RIBA II (Chiron Corporation, Emeryville, CA). One hundred male patients consecutively admitted to an alcoholic rehabilitation program were included. Group 1 was comprised of 40 patients with clinically apparent liver disease. Group 2 was comprised of 60 patients without clinically apparent liver disease. Anti-HCV was performed by a second-generation ELISA assay and confirmed by RIBA II. HCV RNA was performed by Quantiplex assay (Chiron Corporation) and a nested reverse transcriptase-polymerase chain reaction. No significant differences were found between the two groups with regards to age, quantity and duration of alcohol intake, or accepted risk factors for HCV. The overall prevalence of anti-HCV in our patients was 23%, with 43% of these in group 1 and 10% in group 2. HCV RNA tested positive in 94% of the anti-HCV-positive patients in group 1 and in 67% of the anti-HCV-positive patients in group 2. These data suggest that HCV infection is an important cofactor in the pathogenesis of liver disease among alcoholic patients.

Actinomycete culture LL-D37187 has been found to produce the new polyether antibiotic martinomycin. Taxonomic studies, including morphological, physiological, and cell wall chemistry analyses, revealed that culture LL-D37187 is a novel streptomycete species, and the proposed name is Streptomyces salvialis. Martinomycin exhibits activity against the Southern Army Worm (Spodoptera eridania) and Gram-positive bacteria.

Undercompliance with sunscreen reapplication recommendations is a probable factor in suboptimal childhood ultraviolet radiation (UVR) protection. However, improving on the ability of sunscreens to absorb UVR without requiring frequent reapplication is difficult because the models most frequently used to develop and evaluate photoprotectants have only a limited ability to incorporate behavioral and environmental variables that are primarily responsible for loss of sunscreen efficacy. Hence, the objective of the present work was to develop a method to evaluate the efficacy of various regimens of sunscreen reapplication in children, under conditions of unrestricted behavior and exposure to ambient sunlight. Ninety-eight children, ages 7-12, Fitzpatrick skin types I-III, were divided between two study groups. The majority were types I-II, and all types were approximately equally represented between the groups. The children received single or multiple applications of a sun protection factor 25 sunscreen to preassigned lateral halves of the body and engaged in unrestricted activities throughout a 6- (group I) or 8-h (group II) period of sun exposure at a seaside location. The end measurement for these studies was incidence and severity of erythema 18 to 22 h after peak UV exposure. The results obtained showed that 1 or 4 sunscreen applications yielded comparable erythema protection after a 6-hour sun exposure, totaling 13 minimal erythema doses (MED). However, after an 8-h, 21 MED exposure, incidence and severity of erythema was greater at body sites treated with 1 compared with 5 sunscreen applications.(ABSTRACT TRUNCATED AT 250 WORDS)

We show how fast-Fourier-transform methods can be used to accelerate computations of scattering and absorption by particles of arbitrary shape using the discrete-dipole approximation.

The producing organism for the new broad spectrum glycocinnamoylspermidine antibiotics designated LL-BM123beta, gamma1 and gamma2 was characterized as a Nocardia sp. by chemical analysis of the cell wall, growth requirements, morphology and physiological reactions. Fermentation conditions to elaborate and analytical methods to characterize these antibiotics in fermentation filtrates are described.

The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.

The biosynthesis of LL-F28249 alpha in a culture of Streptomyces cyaneogriseus has been studied using 13C, 14C and 18O labeled precursors. A complete 13C NMR spectrum of F28249 alpha has been assigned. Incorporation studies using 13C labeled precursors indicate that the carbon skeleton of F28249 alpha is derived from seven acetate, six propionate and one 2-methylpropionate units. The origin of the oxygen atoms of F28249 alpha has been examined by feeding [1-13C,18O2]acetate, [1-13C,18O2]propionate, [2-13C]acetate/18O2 and 18O2 separately to the fermentation culture and analyzing the resulting labeled LL-F28249 alpha samples by 13C NMR, electron impact MS and chemical ionization MS. Out of a total of eight oxygen atoms in LL-F28249 alpha, four oxygen atoms are derived from acetate, three from propionate and one from molecular oxygen.

9alpha-Fluorohydrocortisone is hydroxylated by Streptomyces roseochromogenes in the 16alpha-, the 2beta-, and in both the 16alpha- and 2beta- positions. 16alpha-Hydroxylation appears to be the more predominant and rapid pathway of transformation. The degree of 2beta-hydroxylation is dependent upon the strain used and may be increased to the point of its being a major route or virtually eliminated by the proper selection of isolates.

A number of nitriles and cyano compounds inhibited chlorination by Streptomyces aureofaciens. In most cases, this inhibition was enhanced by bromide. Methylene blue and p-amino-propiophenone reversed the inhibition to some extent.