Are Antimotility Agents Safe for Use in Clostridioides difficile Infections? Results From an Observational Study in Malignant Hematology Patients.

OBJECTIVES: To evaluate the safety of antimotility agents (AAs) in a population of patients with hematologic malignancies and concurrent Clostridioides difficile infection (CDI) and to describe the outcomes of AA use in a hospital setting. PATIENTS AND METHODS: We used the electronic health record to identify patients who were hospitalized in the adult malignant hematology service who had 1 or more toxin-positive C difficile stool assay between April 1, 2012, and September 21, 2017. We reviewed medical charts to obtain information on the use of AAs and any subsequent gastrointestinal complications. RESULTS: There were 339 patients who were stool toxin positive for CDI during the study period. Of those, 94 patients (27%) were prescribed AAs within 14 days of CDI diagnosis. All patients received CDI antimicrobial therapy within the first 24 hours. There were 2 adverse gastrointestinal events in the group that received AAs and 6 in the group that did not receive AAs. The risk of adverse events did not differ between patients who received AAs and those who did not (adjusted odds ratio, 0.36; 95% CI, 0.06 to 2.10). The mean age of the full cohort was 52.7±15.5 years, and the mean length of stay was 26.7±22.6 days. Early AA use (<48 hours of diagnosis) was not associated with increased adverse effects. CONCLUSION: There was no increase in the incidence of gastrointestinal events in the arm that used AAs compared with the control arm. The evidence suggests that for patients with hematologic malignancies and CDI, the addition of AAs to appropriate antimicrobial therapy poses no additional risk.

Reducing Unnecessary Treatment of Asymptomatic Elevated Blood Pressure with Intravenous Medications on the General Internal Medicine Wards: A Quality Improvement Initiative.

BACKGROUND: Asymptomatic elevated blood pressure (BP) is common in the hospital. There is no evidence supporting the use of intravenous (IV) antihypertensives in this setting. OBJECTIVE: To determine the prevalence and effects of treating asymptomatic elevated BP with IV antihypertensives and to investigate the efficacy of a quality improvement (QI) initiative aimed at reducing utilization of these medications. DESIGN: Retrospective cohort study. SETTING: Urban academic hospital. PATIENTS: Patients admitted to the general medicine service, including the intensive care unit (ICU), with ≥1 episode of asymptomatic elevated BP (>160/90 mm Hg) during hospitalization. INTERVENTION: A two-tiered, QI initiative. MEASUREMENTS: The primary outcome was the monthly proportion of patients with asymptomatic elevated BP treated with IV labetalol or hydralazine. We also analyzed median BP and rates of balancing outcomes (ICU transfers, rapid responses, cardiopulmonary arrests). RESULTS: We identified 2,306 patients with ≥1 episode of asymptomatic elevated BP during the 10-month preintervention period, of which 251 (11%) received IV antihypertensives. In the four-month postintervention period, 70 of 934 (7%) were treated. The odds of being treated were 38% lower in the postintervention period after adjustment for baseline characteristics, including length of stay and illness severity (OR = 0.62; 95% CI 0.47-0.83; P = .001). Median SBP was similar between pre- and postintervention (167 vs 168 mm Hg; P = .78), as were the adjusted proportions of balancing outcomes. CONCLUSIONS: Hospitalized patients with asymptomatic elevated BP are commonly treated with IV antihypertensives, despite the lack of evidence. A QI initiative was successful at reducing utilization of these medications.

Central Venous Catheter Retention and Mortality in Children With Candidemia: A Retrospective Cohort Analysis.

BACKGROUND: Candidemia causes significant morbidity and mortality among children. Removal of a central venous catheter (CVC) is often recommended for adults with candidemia to reduce persistent and metastatic infection. Pediatric-specific data on the impact of CVC retention are limited. METHODS: A retrospective cohort study of inpatients <19 years with candidemia at the Children's Hospital of Philadelphia between 2000 and 2012 was performed. The final cohort included patients that had a CVC in place at time of blood culture and retained their CVC at least 1 day beyond the blood culture being positive. A structured data collection instrument was used to retrieve patient data. A discrete time failure model, adjusting for age and the complexity of clinical care before onset of candidemia, was used to assess the association of CVC retention and 30-day all-cause mortality. RESULTS: Two hundred eighty-five patients with candidemia and a CVC in place at the time of blood culture were identified. Among these 285 patients, 30 (10%) died within 30 days. Central venous catheter retention was associated with a significant increased risk of death on a given day (odds ratio, 2.50; 95% confidence interval, 1.06-5.91). CONCLUSIONS: Retention of a CVC was associated with an increased risk of death after adjusting for age and complexity of care at candidemia onset. Although there is likely persistence of unmeasured confounding, given the strong association between catheter retention and death, our data suggest that early CVC removal should be strongly considered.

Pediatric Risk Factors for Candidemia Secondary to Candida glabrata and Candida krusei Species.

This 13-year retrospective study investigated risk factors for candidemia secondary to Candida species with increased likelihood of fluconazole resistance. Of 344 candidemia cases, 23 were caused by C glabrata or C krusei (CGCK). Age >2 years, recent fluconazole exposure, and recent surgery were independent risk factors for CGCK.

Trends in zygomycosis in children.

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.

Variability in antibiotic use at children's hospitals.

BACKGROUND: Variation in medical practice has identified opportunities for quality improvement in patient care. The degree of variation in the use of antibiotics in children's hospitals is unknown. METHODS: We conducted a retrospective cohort study of 556,692 consecutive pediatric inpatient discharges from 40 freestanding children's hospitals between January 1, 2008, and December 31, 2008. We used the Pediatric Health Information System to acquire data on antibiotic use and clinical diagnoses. RESULTS: Overall, 60% of the children received at least 1 antibiotic agent during their hospitalization, including >90% of patients who had surgery, underwent central venous catheter placement, had prolonged ventilation, or remained in the hospital for >14 days. Even after adjustment for both hospital- and patient-level demographic and clinical characteristics, antibiotic use varied substantially across hospitals, including both the proportion of children exposed to antibiotics (38%-72%) and the number of days children received antibiotics (368-601 antibiotic-days per 1000 patient-days). In general, hospitals that used more antibiotics also used a higher proportion of broad-spectrum antibiotics. CONCLUSIONS: Children's hospitals vary substantially in their use of antibiotics to a degree unexplained by patient- or hospital-level factors typically associated with the need for antibiotic therapy, which reveals an opportunity to improve the use of these drugs.

Risk factors and predictors for candidemia in pediatric intensive care unit patients: implications for prevention.

BACKGROUND: Candida species are the leading cause of invasive fungal infections in hospitalized children and are the third most common isolates recovered from patients with healthcare-associated bloodstream infection in the United States. Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients. METHODS: We conducted a population-based case-control study of PICU patients at Children's Hospital of Philadelphia during the period from 1997 through 2004. Case patients were identified using laboratory records, and control patients were selected from PICU rosters. Control patients were matched to case patients by incidence density sampling, adjusting for time at risk. Following conditional multivariate analysis, we performed weighted multivariate analysis to determine predicted probabilities for candidemia given certain risk factor combinations. RESULTS: We identified 101 case patients with candidemia (incidence, 3.5 cases per 1000 PICU admissions). Factors independently associated with candidemia included presence of a central venous catheter (odds ratio [OR], 30.4; 95% confidence interval [CI], 7.7-119.5), malignancy (OR, 4.0; 95% CI, 1.23-13.1), use of vancomycin for >3 days in the prior 2 weeks (OR, 6.2; 95% CI, 2.4-16), and receipt of agents with activity against anaerobic organisms for >3 days in the prior 2 weeks (OR, 3.5; 95% CI, 1.5-8.4). Predicted probability of having various combinations of the aforementioned factors ranged from 10.7% to 46%. The 30-day mortality rate was 44% among case patients and 14% among control patients (OR, 4.22; 95% CI, 2.35-7.60). CONCLUSIONS: To our knowledge, this is the first study to evaluate independent risk factors and to determine a population of children in PICUs at high risk for developing candidemia. Future efforts should focus on validation of these risk factors identified in a different PICU population and development of interventions for prevention of candidemia in critically ill children.

Zygomycosis in children: a systematic review and analysis of reported cases.

BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.