The reader's ability to judge the validity of pharmacokinetic research can be greatly compromised by the incomplete reporting of study information. Using consensus methods, we have developed a tool to guide transparent and accurate reporting of clinical pharmacokinetic studies. Endorsement and implementation of these guidelines by researchers, clinicians and journals would promote more consistent reporting of these studies and allow for better assessment of utility for clinical applications.
Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.
Vitamin C deficiency in developed countries is typically observed in patients with unique clinical conditions such as cystic fibrosis or anorexia nervosa, or in patients on long-term tube feeds. We report here a clinical observation in six pediatric and adolescent patients (median age 17.5 yr, range 9.8-23.5 yr) with chronic GVHD with mucous membrane involvement found to be vitamin C deficient. These patients' baseline serum vitamin C levels ranged from <0.12 to 0.94 mg/dL (normal value 0.20-1.90 mg/dL), with a mean level 0.56 ± 0.36 mg/dL and a median level 0.6 mg/dL. Among these patients, signs and symptoms of mucositis failed to respond to standard chronic GVHD therapy. After receiving treatment with 2000 mg of ascorbic acid by mouth, daily patients displayed increased serum vitamin C levels. Clinically, this correlated with a remarkable improvement in patients' mucositis and ability to eat.
model (Miller et al., Blood, 2010). Importantly, our results show that LFA-1 expression is highly upregulated in CNS leukocyte infiltrates of animals with untreated GvHD (Figure 2). LFA-1 is an integrin that is critical for leukocyte trafficking into the CNS during demyelinating disease (Hu et al., J Leuk Bio, 2010). These results suggest that the mechanisms of T cell infiltration into the CNS during GVHD may have important similarities to autoimmune-mediated CNS diseases such as multiple sclerosis, and thus may be amenable to targeted therapies such as integrin-blockade. Our findings argue that CNS-GvHD can occur in primates undergoing HCT, and is characterized by an infiltrate of activated, integrin-expressing CD8 T cells. These results underscore the importance of including GVHD in the differential diagnosis of CNS symptoms after HCT, and suggest that targeted therapeutic strategies may be able to address this often under-recognized complication of HCT.
With regard to susceptibility to FQ, 2/19 (10.5%) microbiologically identified organisms in overall FQ cohort were susceptible versus 12/24 (50%) organisms in overall non-FQ cohort (p¼.05). The microbiologically identified organisms were gram negative in 16% of FQ cohort versus 33% of non-FQ cohort (p>.05). Conclusion: FQ prophylaxis post-HCT reduces incidence of bacteremia without increasing CDAD. FQ prophylaxis may lead to higher rates of gram positive and FQ-resistant organisms.
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