Correction to: Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons.

The original version of this article [1], published on 6 February 2018, contains a mistake in the 'Conclusions' section. The corrected version of the affected sentence is given below and the corrected part is marked in bold.

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons.

BACKGROUND: Preliminary evidence suggests that the enteric microbiota may play a role in the expression of neurological symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Overlapping symptoms with the acute presentation of D-lactic acidosis has prompted the use of antibiotic treatment to target the overgrowth of species within the Streptococcus genus found in commensal enteric microbiota as a possible treatment for neurological symptoms in ME/CFS. METHODS: An open-label, repeated measures design was used to examine treatment efficacy and enable sex comparisons. Participants included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces) and with a count greater than 5% of the total count of aerobic microorganisms. The 4-week treatment protocol included alternate weeks of Erythromycin (400 mg of erythromycin as ethyl succinate salt) twice daily and probiotic (D-lactate free multistrain probiotic, 5 × 1010 cfu twice daily). 2 × 2 repeated measures ANOVAs were used to assess sex-time interactions and effects across pre- and post-intervention for microbial, lactate and clinical outcomes. Ancillary non-parametric correlations were conducted to examine interactions between change in microbiota and clinical outcomes. RESULTS: Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). Mood, fatigue and urine D:L lactate ratio remained similar across time. Ancillary results infer that shifts in microbiota were associated with more of the variance in clinical changes for males compared with females. CONCLUSIONS: Results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population. Streptococcus spp. are not the primary or sole producers of D-lactate. Further investigation of lactate concentrations are needed to elucidate any role of D-lactate in this population. Concurrent microbial shifts that may be associated with clinical improvement (i.e., increased Bacteroides and Bifidobacterium or decreased Clostridium in males) invite enquiry into alternative strategies for individualised treatment. Trial Registration Australian and New Zealand Clinical Trial Registry (ACTRN12614001077651) 9th October 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366933&isReview=true.

Evaluation of a novel method for the analysis of alcohol biomarkers: Ethyl glucuronide, ethyl sulfate and phosphatidylethanol.

Currently available markers and methods to evaluate alcohol consumption are indirect and suboptimal, or rely on self-report, which have inherent problems. Direct metabolites of alcohol, phosphatidylethanol (PEth), ethyl sulfate (EtS), and ethyl glucuronide (EtG), are known to improve diagnostic accuracy. In this study, methods were established for the identification of PEth in erythrocytes and EtG and EtS in serum using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The three biomarkers were tested and validated in volunteer teetotalers (n = 4) and drinkers (n = 10), and applied in patients (n = 8) hospitalized with alcohol-related problems. Linearity of each assay was demonstrated from 22.5 to 900 nM for EtG, 40-3175 nM for EtS, and 21-750 nM for PEth. The methods were highly selective, precise (<5% coefficient of variation), and had optimal accuracy (within 10% of the nominal value) for all three analytes. Recovery for all three compounds exceeded 90%. A preliminary investigation into the window of detection of these biomarkers after a single occasion of moderate alcohol consumption revealed that EtG and EtS could be detected and quantified over the short term (days) and PEth over the long term (weeks). All three biomarkers showed high sensitivity and specificity in distinguishing between abstinence and any alcohol use at the cut-off values of 22.5 nM for EtG, 40 nM for EtS, and 21 nM for PEth. We have established simultaneous assays for EtG, EtS, and PEth for routine clinical use in confirming abstinence and exposure, and detecting under-reporting of alcohol use, relevant in clinical and non-clinical settings.

Once-daily intravenous cefazolin plus oral probenecid is equivalent to once-daily intravenous ceftriaxone plus oral placebo for the treatment of moderate-to-severe cellulitis in adults.

A once-daily regimen of cefazolin (2 g intravenously [iv]) plus probenecid (1 g by mouth) was compared with a once-daily regimen of ceftriaxone (1 g iv) plus oral placebo in a randomized, double-blind equivalence trial of home-based therapy for moderate-to-severe cellulitis in adults. For the assessable recipients of cefazolin-probenecid (n=59) and ceftriaxone-placebo (n=57), clinical cure occurred at the end of treatment in 86% and 96% (P=.11), respectively, and was maintained at 1 month of follow-up in 96% and 91% (P=.55), respectively. The mean number of treatment doses (+/-standard deviation) given was similar in the 2 treatment arms (6.97+/-2.6 for cefazolin-probenecid and 6.12+/-2.1 for ceftriaxone-placebo; P=.06). The median antibiotic trough concentrations were 2.35 microgram/mL for cefazolin and 15.45 microgram/mL for ceftriaxone. Patients in the 2 treatment arms were similar with regard to overall rates of adverse reaction (P=.15), but nausea was more common among those in the cefazolin-probenecid arm (P=.048). The once-daily regimen of cefazolin-probenecid is a cheap, practical, and effective treatment option for moderate-to-severe cellulitis, and it avoids the need to use third-generation cephalosporins in most patients.