Whole-genome sequencing of Staphylococcus epidermidis bloodstream isolates from a prospective clinical trial reveals that complicated bacteraemia is caused by a limited number of closely related sequence types.

OBJECTIVES: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia. METHODS: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information. RESULTS: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001). CONCLUSION: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections.

How common is subsequent central nervous system toxicity in asymptomatic patients with haematologic malignancy and supratherapeutic voriconazole serum levels?

OBJECTIVES: We sought to determine the frequency at which patients with elevated voriconazole (VRC) levels but no clinically evident central nervous system (CNS) toxicity subsequently develop CNS toxicity. METHODS: We retrospectively reviewed the records of adult patients with haematolologic malignancy who had a VRC serum level >5.5 µg/mL at MD Anderson Cancer Center (January 2010 to December 2015). Patients with any documented CNS toxicity at the time the VRC level was obtained or patients whose VRC was discontinued as a response to high VRC level were excluded. Neurologic status was assessed using standard grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity. RESULTS: We identified 320 such patients (mean age, 57 ± 15 years; 202 male (63%)). Subsequent CNS toxicity was documented in only 16 patients (5%). The most common CNS toxicities were visual disturbances (9/16, 56%), depressed consciousness (5/16, 31%) and cognitive disturbance (4/16, 19%). Patients with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p 0.08). The use of one or more neurotoxic drugs was common in patients with subsequent CNS toxicity (14/16, 88%). Reduction of VRC dose associated with the high VRC level did not correlate with less subsequent CNS toxicity. CONCLUSIONS: Development of subsequent CNS toxicity is uncommon in haematolologic malignancy patients with elevated VRC levels who had no evidence of toxicity at the time the level was obtained. Automatic reduction of VRC dose out of concern for impending CNS toxicity might not be warranted.

Aerosolized ribavirin: the most expensive drug for pneumonia.

Dramatic, overnight cost increases of important orphan and generic medications have recently come under public and government scrutiny. We highlight the case of aerosolized ribavirin, an important antiviral agent in hematopoietic stem cell transplantation which, because of substantial price increases, may now cost more than the transplant procedure itself.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

BACKGROUND: Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). AIM: To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. METHODS: This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. FINDINGS: In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (P<0.0001, each). Total hospital median LOS and costs increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (P<0.0001, each). The median cost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). CONCLUSION: This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI.

Evaluation of antioxidant and proinflammatory gene expression in bovine mammary tissue during the periparturient period.

The incidence and severity of mastitis can be high during the period of transition from pregnancy to lactation when dairy cattle are susceptible to oxidative stress. Oxidative stress may contribute to the pathogenesis of mastitis by modifying the expression of proinflammatory genes. The overall goal of this study was to determine the relationship between critical antioxidant defense mechanisms and proinflammatory markers in normal bovine mammary tissue during the periparturient period. Mammary tissue samples were obtained from 12 cows at 35, 20, and 7 d before expected calving and during early lactation (EL, 15 to 28 d in milk). Enzyme activities for cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase were relatively low during the dry period, but increased during EL, whereas activity of thioredoxin reductase 1 did not change significantly as a function of time. In contrast, gene expression for these antioxidant selenoproteins and for heme oxygenase-1 gradually decreased as parturition approached and then increased during EL. The expression of intercellular vascular adhesion molecule-1 and vascular cell adhesion molecule-1 followed a similar trend where mRNA abundance gradually declined as parturition approached with a slight rebound in EL. Gene expression of the pro-oxidant, 15-lipoxygenase 1, which is known to increase during times of oxidative stress, also increased dramatically in mammary tissue from EL cows. Expression of the proinflammatory cytokines, IL-1beta, IL-6, and IL-8 did not change significantly during the periparturient period. Strong positive correlations were found between several antioxidant enzymes (cytosolic glutathione peroxidase, thioredoxin reductase 1, and heme oxygenase-1) and vascular adhesion molecules (intercellular vascular adhesion molecule-1, vascular cell adhesion molecule-1) suggesting a protective response of these antioxidants to an enhanced proinflammatory state. Ability to control oxidative stress through manipulation of key antioxidant enzymes in the future may modify the proinflammatory state of periparturient cows and reduce incidence and severity of some diseases such as mastitis.