Risk of Acute Kidney Injury Based on Vancomycin Target Trough Attainment Strategy: Area-Under-the-Curve-Guided Bayesian Software, Nomogram, or Trough-Guided Dosing.

BACKGROUND: Guidelines support area-under-the-curve (AUC) monitoring for vancomycin dosing which may lower overall doses and reduce acute kidney injury (AKI). OBJECTIVE: The aim of this study was to compare incidence of AKI across 3 vancomycin dosing modalities: AUC-targeted Bayesian pharmacokinetic software, AUC-targeted empiric dosing nomogram, and trough-guided dosing using clinical pharmacists' judgment. METHODS: This retrospective study included adult patients with a pharmacy dosing consult who received ≥1 dose of vancomycin and ≥1 serum vancomycin level documented between January 1, 2018, and December 31, 2019. Patients with baseline serum creatinine ≥2 mg/dL, weight ≥100 kg, receiving renal replacement therapy, AKI prior to vancomycin therapy, or vancomycin ordered only for surgical prophylaxis were excluded. The primary analysis was incidence of AKI adjusted for baseline serum creatinine, age, and intensive care unit admission. A secondary outcome was adjusted incidence of an abnormal trough value (<10 or >20 µg/mL). RESULTS: The study included 3459 encounters. Incidence of AKI was 21% for Bayesian software (n = 659), 22% for the nomogram (n = 303), and 32% for trough-guided dosing (n = 2497). Compared with trough-guided dosing, incidence of AKI was lower in the Bayesian (adjusted odds ratio [OR] = 0.72, 95% confidence interval [CI]: 0.58-0.89) and the nomogram (adjusted OR = 0.71, 95% CI: 0.53-0.95) groups. Compared with trough-guided dosing, abnormal trough values were less common in the Bayesian group (adjusted OR = 0.83, 95% CI: 0.69-0.98). CONCLUSION AND RELEVANCE: Study results suggest that use of AUC-guided Bayesian software reduces the incidence of AKI and abnormal trough values compared with trough-guided dosing.

Successful Treatment of Invasive Mucormycosis in Orthotopic Liver Transplant Population.

Mucormycosis is caused by ubiquitous fungi and encompasses a variety of different opportunistic syndromes in humans that disproportionately affect immunocompromised patients. Mortality has been documented to range between 50 and 100%; however, location of infection greatly dictates likelihood of survival. Treatment of mucormycosis involves aggressive surgical intervention and combination therapy of antifungal agents. In solid organ transplant recipients, immunosuppressive agents used to prevent rejection of the transplanted organ pose additional obstacles in the treatment of invasive fungal infections. We report on 3 high models for end-stage liver disease (MELD-Na) score orthotopic liver transplant (OLT) recipients who all were diagnosed with Rhizopus spp. infections with positive, 1-year outcomes after aggressive, individualized treatment.

Significant Publications on Infectious Diseases Pharmacotherapy in 2019.

PURPOSE: To provide a summary of the most prominent peer-reviewed infectious diseases (ID) pharmacotherapy and Human Immunodeficiency Virus (HIV)-related articles published in 2019. SUMMARY: Houston Infectious Diseases Network (HIDN) members were asked to nominate articles that they believed were most influential within the ID and HIV pharmacotherapy science communities. A total of 48 general ID and 6 HIV-related articles were nominated. Following nominations, an online survey was distributed via e-mail to Society of Infectious Diseases Pharmacists (SIDP) members, with a total of 156 and 54 members voting for general ID and HIV-related articles, respectively. The results of this survey were ranked to determine the top 10 general ID and top HIV articles. The top articles were then summarized by HIDN members, including residents, fellows, and clinical pharmacists. CONCLUSION: This review covers many of the most influential ID articles published in 2019, including 3 practice guideline updates. Due to the high rate of ID literature published each year, this review continues to help summarize these articles for the ID community, allowing clinicians to remain up-to-date on practice-changing publications in ID and HIV pharmacotherapy.

Genome wide association study identifies novel single nucleotide polymorphic loci and candidate genes involved in soybean sudden death syndrome resistance.

Fusarium virguliforme is a soil borne root pathogen that causes sudden death syndrome (SDS) in soybean [Glycine max (L.) Merrill]. Once the fungus invades the root xylem tissues, the pathogen secretes toxins that cause chlorosis and necrosis in foliar tissues leading to defoliation, flower and pod drop and eventually death of plants. Resistance to F. virguliforme in soybean is partial and governed by over 80 quantitative trait loci (QTL). We have conducted genome-wide association study (GWAS) for a group of 254 plant introductions lines using a panel of approximately 30,000 SNPs and identified 19 single nucleotide polymorphic loci (SNPL) that are associated with 14 genomic regions encoding foliar SDS and eight SNPL associated with seven genomic regions for root rot resistance. Of the identified 27 SNPL, six SNPL for foliar SDS resistance and two SNPL for root rot resistance co-mapped to previously identified QTL for SDS resistance. This study identified 13 SNPL associated with eight novel genomic regions containing foliar SDS resistance genes and six SNPL with five novel regions for root-rot resistance. This study identified five genes carrying nonsynonymous mutations: (i) three of which mapped to previously identified QTL for foliar SDS resistance and (ii) two mapped to two novel regions containing root rot resistance genes. Of the three genes mapped to QTL for foliar SDS resistance genes, two encode LRR-receptors and third one encodes a novel protein with unknown function. Of the two genes governing root rot resistance, Glyma.01g222900.1 encodes a soybean-specific LEA protein and Glyma.10g058700.1 encodes a heparan-alpha-glucosaminide N-acetyltransferase. In the LEA protein, a conserved serine residue was substituted with asparagine; and in the heparan-alpha-glucosaminide N-acetyltransferase, a conserved histidine residue was substituted with an arginine residue. Such changes are expected to alter functions of these two proteins regulated through phosphorylation. The five genes with nonsynonymous mutations could be considered candidate SDS resistance genes and should be suitable molecular markers for breeding SDS resistance in soybean. The study also reports desirable plant introduction lines and novel genomic regions for enhancing SDS resistance in soybean.

Mapping of new quantitative trait loci for sudden death syndrome and soybean cyst nematode resistance in two soybean populations.

KEY MESSAGE: Novel QTL conferring resistance to both the SDS and SCN was detected in two RIL populations. Dual resistant RILs could be used in breeding programs for developing resistant soybean cultivars. Soybean cultivars, susceptible to the fungus Fusarium virguliforme, which causes sudden death syndrome (SDS), and to the soybean cyst nematode (SCN) (Heterodera glycines), suffer yield losses valued over a billion dollars annually. Both pathogens may occur in the same production fields. Planting of cultivars genetically resistant to both pathogens is considered one of the most effective means to control the two pathogens. The objective of the study was to map quantitative trait loci (QTL) underlying SDS and SCN resistances. Two recombinant inbred line (RIL) populations were developed by crossing 'A95-684043', a high-yielding maturity group (MG) II line resistant to SCN, with 'LS94-3207' and 'LS98-0582' of MG IV, resistant to both F. virguliforme and SCN. Two hundred F7 derived recombinant inbred lines from each population AX19286 (A95-684043 × LS94-3207) and AX19287 (A95-684043 × LS98-0582) were screened for resistance to each pathogen under greenhouse conditions. Five hundred and eighty and 371 SNP markers were used for mapping resistance QTL in each population. In AX19286, one novel SCN resistance QTL was mapped to chromosome 8. In AX19287, one novel SDS resistance QTL was mapped to chromosome 17 and one novel SCN resistance QTL was mapped to chromosome 11. Previously identified additional SDS and SCN resistance QTL were also detected in the study. Lines possessing superior resistance to both pathogens were also identified and could be used as germplasm sources for breeding SDS- and SCN-resistant soybean cultivars.

Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers.

BACKGROUND/PURPOSE: Ethanol coadministered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects. We asked the question: Are these ethanol-MPH interactions based more fundamentally on (1) inhibition of postabsorption d-MPH metabolism or (2) acceleration of MPH formulation gastric dissolution by ethanol in the stomach? This was investigated using the pulsatile, distinctly biphasic, spheroidal oral drug absorption systems of dl-MPH and d-MPH. METHODS: In a randomized, 4-way crossover study, 14 healthy subjects received pulsatile dl-MPH (40 mg) or d-MPH (20 mg), with or without ethanol (0.6 g/kg), dosed 4 hours later. These 4 hours allowed the delayed-release second MPH pulse to reach a more distal region of the gut to preclude gastric biopharmaceutical influences. Plasma was analyzed using a highly sensitive chiral method. Subjective/physiological effects were recorded. FINDINGS/RESULTS: Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01) and the partial area under the plasma concentration curve from 4 to 8 hours by 25% (P < 0.05). The respective values for enantiopure d-MPH were 27% (P = 0.001) and 20% (P < 0.01). The carboxylesterase 1-mediated transesterification metabolite ethylphenidate served as a biomarker for coexposure. Ethanol significantly potentiated stimulant responses to either formulation. IMPLICATIONS/CONCLUSIONS: These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations. Understanding the pharmacology underlying the frequent coabuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid attention-deficit/hyperactivity disorder-alcohol use disorder.