A Novel Clinical Grading Scale to Guide the Management of Crusted Scabies

BackgroundCrusted scabies, or hyperinfestation with Sarcoptes scabiei, occurs in people with an inadequate immune response to the mite. In recent decades, data have emerged suggesting that treatment of crusted scabies with oral ivermectin combined with topical agents leads to lower mortality, but there are no generally accepted tools for describing disease severity. Here, we describe a clinical grading scale for crusted scabies and its utility in real world practice.Methodology/Principal FindingsIn 2002, Royal Darwin Hospital (RDH), a hospital in tropical Australia developed and began using a clinical grading scale to guide the treatment of crusted scabies. We conducted a retrospective observational study including all episodes of admission to RDH for crusted scabies during the period October 2002–December 2010 inclusive. Patients who were managed according to the grading scale were compared with those in whom the scale was not used at the time of admission but was calculated retrospectively. There were 49 admissions in 30 patients during the study period, of which 49 (100%) were in Indigenous Australians, 29 (59%) were male and the median age was 44.1 years. According to the grading scale, 8 (16%) episodes were mild, 24 (49%) were moderate, and 17 (35%) were severe. Readmission within the study period was significantly more likely with increasing disease severity, with an odds ratio (95% CI) of 12.8 (1.3–130) for severe disease compared with mild. The patients managed according to the grading scale (29 episodes) did not differ from those who were not (20 episodes), but they received fewer doses of ivermectin and had a shorter length of stay (11 vs. 16 days, p = 0.02). Despite this the outcomes were no different, with no deaths in either group and a similar readmission rate.Conclusions/SignificanceOur grading scale is a useful tool for the assessment and management of crusted scabies

Treatment of Herpes Simplex Virus Type 2 Meningitis:A Survey Among Infectious Diseases Specialists in France, Sweden, Australia, and Denmark

BACKGROUND: We aimed to describe attitudes toward treatment of herpes simplex virus type 2 (HSV-2) meningitis and prioritize future trials. METHODS: This was a self-administered online survey of HSV-2 meningitis treatment among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark. RESULTS: A total of 223 ID specialists (45% female) from France (36%), Denmark (24%), Sweden (21%), and Australia (19%) participated in the survey, primarily from university hospitals (64%). The estimated overall response rate was 11% and ranged from 6% (Australia) to 64% (Denmark). Intravenous (IV) acyclovir followed by oral valacyclovir was the favored treatment in 110 of 179 (61%), whereas monotherapy with either IV acyclovir or oral valacyclovir was used by 35 of 179 (20%) and 34 of 179 (19%), respectively. The median total duration was reported to be 7 days (interquartile range, 7–10 days) regardless of antiviral regimen. Immunocompromise influenced decisions on antiviral treatment in 110 of 189 (58%) of respondents, mainly by prolonged total duration of treatment (36/110 [33%]), prolonged IV administration (31/110 [28%]), and mandatory antiviral treatment (25/110 [23%]). Treatment with acyclovir/valacyclovir versus placebo and comparison of acyclovir versus valacyclovir were assigned the highest prioritization scores for future randomized controlled trials on HSV-2 meningitis. CONCLUSIONS: Perceptions of indications for as well as type and duration of antiviral treatment varied substantially among ID specialists

Rapid Detection of the H275Y Oseltamivir Resistance Mutation in Influenza A/H1N1 2009 by Single Base Pair RT-PCR and High-Resolution Melting

Introduction: We aimed to design a real-time reverse-transcriptase-PCR (rRT-PCR), high-resolution melting (HRM) assay to detect the H275Y mutation that confers oseltamivir resistance in influenza A/H1N1 2009 viruses.Findings: A novel strategy of amplifying a single base pair, the relevant SNP at position 823 of the neuraminidase gene, was chosen to maintain specificity of the assay. Wildtype and mutant virus were differentiated when using known reference samples of cell-cultured virus. However, when dilutions of these reference samples were assayed, amplification of nonspecific primer-dimer was evident and affected the overall melting temperature (Tm) of the amplified products. Due to primer-dimer appearance at .30 cycles we found that if the cycle threshold (CT) for a dilution was .30, the HRM assay did not consistently discriminate mutant from wildtype. Where the CT was ,30 we noted an inverse relationship between CT and Tm and fitted quadratic curves allowed the discrimination of wildtype, mutant and 30:70 mutant:wildtype virus mixtures. We compared the CT values for a TaqMan H1N1 09 detection assay with those for the HRM assay using 59 clinical samples and demonstrated that samples with a TaqMan detection assay CT.32.98 would have an H275Y assay CT.30. Analysis of the TaqMan CT values for 609 consecutive clinical samples predicted that 207 (34%) of the samples would result in an HRM assay CT.30 and therefore not be amenable to the HRM assay.Conclusions: The use of single base pair PCR and HRM can be useful for specifically interrogating SNPs. When applied to H1N1 09, the constraints this placed on primer design resulted in amplification of primer-dimer products. The impact primer-dimer had on HRM curves was adjusted for by plotting Tm against CT. Although less sensitive than TaqMan assays, the HRM assay can rapidly, and at low cost, screen samples with moderate viral concentrations

Is Streptococcus pyogenes resistant or susceptible to Trimethoprim-Sulfamethoxazole?

Streptococcus pyogenes is commonly believed to be resistant to trimethoprim-sulfamethoxazole (SXT), resulting in reservations about using SXT for skin and soft tissue infections (SSTI) where S. pyogenes is involved. S. pyogenes\u27 in vitro susceptibility to SXT depends on the medium\u27s thymidine content. Thymidine allows S. pyogenes to bypass the sulfur-mediated inhibition of folate metabolism and, historically, has resulted in apparently reduced susceptibility of S. pyogenes to sulfur antibacterials. The low thymidine concentration in Mueller-Hinton agar (MHA) is now regulated. We explored S. pyogenes susceptibility to SXT on various media. Using two sets of 100 clinical S. pyogenes isolates, we tested for susceptibility using SXT Etests on MHA containing defibrinated horse blood and 20 mg/liter β-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA). European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints defined susceptibility (MIC, ≤1 mg/liter) and resistance (MIC, >2 mg/liter). In study 1, 99% of S. pyogenes isolates were susceptible to SXT on MHA, MHBA, and MHLHBA, with geometric mean MICs of 0.04, 0.04, and 0.05 mg/liter, respectively. In study 2, all 100 S. pyogenes isolates were susceptible to SXT on MHF, MHS, MHA, and MHLHBA with geometric mean MICs of 0.07, 0.16, 0.07, and 0.09 mg/liter, respectively. This study confirms the in vitro susceptibility of S. pyogenes to SXT, providing support for the use of SXT for SSTIs. A clinical trial using SXT for impetigo is ongoing