A Multicenter Study of Bacterial Blood Stream Infections in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients: The Role of Acute Gastrointestinal Graft-versus-Host Disease.

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.

Risk Factors and Utility of a Risk-Based Algorithm for Monitoring Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections in Pediatric Recipients after Allogeneic Hematopoietic Cell Transplantation.

Infectious complications, particularly viral infections, remain a significant cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). Only a handful of studies in children have analyzed the risks for and impact of viremia on alloHCT-related outcomes. We conducted a retrospective study of 140 pediatric patients undergoing alloHCT to investigate the incidence of and risk factors for cytomegalovirus (CMV), adenovirus (ADV), and Epstein-Barr virus (EBV) viremia and viral disease after alloHCT. Furthermore, we assessed the impact of viremia on days of hospitalization and develop an algorithm for routine monitoring of viremia. Patients were monitored before alloHCT and then weekly for 180 days after alloHCT. Patients were considered to have viremia if CMV were > 600 copies/mL, EBV were > 1000 copies/mL, or ADV were > 1000 copies/mL on 2 consecutive PCRs. The overall incidences of viremia and viral disease in all patients from day 0 to +180 after alloHCT were 41.4% (n = 58) and 17% (n = 24), respectively. The overall survival for patients with viremia and viral disease was significantly lower compared with those without viremia (58% versus 74.2%, P = .03) and viral disease (48.2% versus 71.2%, P = .024). We identified that pretransplantation CMV risk status, pre-alloHCT viremia, and use of alemtuzumab were associated with the risk of post-alloHCT viremia. The average hospitalization days in patients with CMV risk (P = .011), viremia (P = .024), and viral disease (P = .002) were significantly higher. The algorithm developed from our data can potentially reduce viral PCR testing by 50% and is being studied prospectively at our center. Improved preventative treatment strategies for children at risk of viremia after alloHCT are needed.

Acute gastrointestinal graft-vs-host disease is associated with increased enteric bacterial bloodstream infection density in pediatric allogeneic hematopoietic cell transplant recipients.

BACKGROUND: Bacterial septicemia remains the leading cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (AlloHCT). While murine studies have found acute gastrointestinal graft-vs-host disease (aG-GVHD) to be associated with increased incidence of enteric bacterial bloodstream infections (EB-BSI), this association has not been studied in humans. We hypothesized that in patients who developed aG-GVHD, the EB-BSI density after onset of aG-GVHD would be higher than before onset and higher than in patients without acute GVHD (aGVHD). METHODS: We retrospectively reviewed data collected on 264 pediatric AlloHCT recipients with malignant and nonmalignant disease. We calculated and compared EB-BSI densities in the following 3 subgroups: patients without aGVHD and patients with aG-GVHD, both before and after onset of aG-GVHD. We also examined the effect of aG-GVHD onset on the first episode of EB-BSI using Cox proportional hazards models. RESULTS: The overall incidence of aG-GVHD was 28.8% (n = 76). Analyses done both at 120 and 180 days post-AlloHCT showed that the EB-BSI density increased after aG-GVHD onset (0.95 infections/person-year before aG-GVHD vs 2.7 infections/person-year after aG-GVHD at day 120 [P = .006]; 0.95 infections/person-year before aG-GVHD vs 2.26 infections/person-year after aG-GVHD at day 180 [P = .033]). On multivariate analysis, the onset of aG-GVHD had a positive hazard ratio of 1.47 (P = .077) on time to first EB-BSI. CONCLUSIONS: Our results support the theory that aG-GVHD predisposes pediatric AlloHCT recipients to EB-BSI. Prophylactic agents such as probiotics should be studied prospectively in patients with aG-GVHD.

Human herpesvirus-6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation.

HHV-6 is an evolving pathogen in the field of AlloHCT. However, the impact of HHV-6 on AlloHCT outcomes remains to be elucidated. We studied the incidence and clinical impact of HHV-6 viremia in children following AlloHCT. One hundred consecutive children were monitored weekly by plasma PCR for the first 180 days following AlloHCT for HHV-6, CMV, EBV, and ADV. HHV-6 viremia was defined as plasma PCR >1000 viral copies/mL. The median age was nine yr. Following AlloHCT, 19% (95% CI 11.3-26.7%) of patients had HHV-6 viremia, with the highest incidence of reactivation (14/19, 73%) occurring during day +15-day +98. The proportion of platelet engraftment by day +180 was lower in patients with HHV-6 viremia (58%) than in those without HHV-6 viremia (82%), p = 0.028. Delay in neutrophil and platelet engraftment was not associated with HHV-6 viremia in multivariate analysis. Similarly, HHV-6 viremia was not associated with TRM in multivariate analysis (p = 0.15). In summary, HHV-6 viremia is prevalent in pediatric AlloHCT recipients. Based on our study results, we recommend that HHV-6 PCR should only be performed on clinical suspicion.

Surgical and Medical Management of Purulent Bacterial Pericarditis With Pericardial Mass in a Young Child.

Purulent bacterial pericarditis is rare and associated with significant short- and long-term morbidity. We report a case of purulent bacterial pericarditis caused by Group A Streptococcus in an immunocompetent young child presenting with a pericardial mass. She was successfully treated with a combined medical and early surgical approach. (Level of Difficulty: Intermediate.).

Early increases in concentrations of total, LDL, and HDL cholesterol in HIV-infected children following new exposure to antiretroviral therapy.

Antiretroviral therapy (ART) is associated with dyslipidemia and cardiovascular disease in adults infected with HIV. For children perinatally infected with HIV, ART exposure is lifelong and early-onset dyslipidemia could have significant long-term effects. We examined cholesterol levels in children during the first year after exposure to a new ART regimen (initiation or switch). In 52 children, total cholesterol increased by 30.5 and 43 mg/dL at 6 and 12 months, respectively (P < 0.001). Low-density lipoprotein cholesterol made the largest contribution, but high-density lipoprotein cholesterol also increased within months of therapy alteration. Early identification of these children and intervention could mediate potential increased risk for future cardiovascular disease.

Bacterial bloodstream infections in pediatric allogeneic hematopoietic stem cell recipients before and after implementation of a central line-associated bloodstream infection protocol: A single-center experience.

INTRODUCTION: There are only few reports describing the influence of central line-associated bloodstream infection (CLABSI) prevention strategies on the incidence of bacterial bloodstream infections (BBSIs). METHODS: We performed a retrospective cohort study among pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) to assess potential changes in BBSI rates during 3 time periods: pre-CLABSI prevention era (era 1, 2004-2005), CLABSI prevention implementation era (era 2, 2006-2009), and maintenance of CLABSI prevention era (era 3, 2010-2012). BBSI from day 0-365 following allo-HCT were studied. The comparison of person-years incidence rates among different periods was carried out by Poisson regression analysis. RESULTS: The mean age of patients was 10.0 years. During the study period, 126 (65%) of 190 patients had at least a single BBSI. From day 0-30, day 31-100, day 101-180, and day 181-365, 20%, 28%, 30%, and 17% of patients, respectively, experienced BBSIs. The rate of Staphylococcus epidermidis and gram-negative pathogens significantly declined from 3.16-0.93 and 6.32-2.21 per 100 person-months during era 1 and era 3, respectively (P = .001). CONCLUSIONS: Patients undergoing allo-HCT during era 3 were associated with decreased risk of BBSI (P = .012). Maintenance of CLABSI protocols by nursing staff and appropriate education of other care providers is essential to lower incidence of BBSI in this high-risk population, and further strategies to decrease infection burden should be studied.

Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents.

BACKGROUND: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment. METHODS: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes. FINDINGS: Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and >10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values. INTERPRETATION: Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.

Pseudomonas aeruginosa infections in the neonatal intensive care unit.

Pseudomonas aeruginosa is a highly adaptable gram-negative bacillus with the ability to cause serious disease in vulnerable populations. This article reviews the relevant epidemiology of this pathogen in the hospital setting with particular attention to the neonatal unit. Issues related to reservoirs of the organism with special consideration of the hands of staff are also addressed. Virulence factors and pathogenic mechanisms are highlighted as well as the important role of antimicrobial resistance patterns. Finally, there is a discussion of the clinical syndromes found in neonates and the appropriate antibiotic usage strategies for effective treatment of this pathogen of continuing importance.