Christopher J. Russell

The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review

BackgroundVentilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines.MethodsWe conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook’s “Risk of Bias” assessment tool.ResultsSix studies met full inclusion criteria. For the systemic review’s primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis.ConclusionsThere is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled antibiotic therapy for VAP and VAT.

Differences in the Expressed HLA Class I Alleles Effect the Differential Clustering of HIV Type 1-Specific T Cell Responses in Infected Chinese and Caucasians

China is a region of the world with a rapidly spreading HIV-1 epidemic. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to support the design and testing of an effective HIV-1 vaccine for this population. HIV-1-specific T cell responses were characterized in 32 HIV-1-infected individuals of Chinese origin and compared to 34 infected caucasians using 410 overlapping peptides spanning the entire HIV-1 clade B consensus sequence in an IFN-gamma ELISpot assay. All HIV-1 proteins were targeted with similar frequency in both populations and all study subjects recognized at least one overlapping peptide. HIV-1-specific T cell responses clustered in seven different regions of the HIV-1 genome in the Chinese cohort and in nine different regions in the caucasian cohort. The dominant HLA class I alleles expressed in the two populations differed significantly, and differences in epitope clustering pattern were shown to be influenced by differences in class I alleles that restrict immunodominant epitopes. These studies demonstrate that the clustering of HIV-1-specific T cell responses is influenced by the genetic HLA class I background in the study populations. The design and testing of candidate vaccines to fight the rapidly growing HIV-1 epidemic must therefore take the HLA genetics of the population into account as specific regions of the virus can be expected to be differentially targeted in ethnically diverse populations.

Pseudomonas aeruginosa and post-tracheotomy bacterial respiratory tract infection readmissions

Identify risk factors for readmission due to a bacterial tracheostomy‐associated respiratory tract infection (bTARTI) within 12 months of discharge after tracheotomy.

Care Variations and Outcomes for Children Hospitalized With Bacterial Tracheostomy-Associated Respiratory Infections.

OBJECTIVES Identify hospital-level care variations and association with length of stay (LOS) and hospital revisit in children with tracheostomies hospitalized for bacterial respiratory tract infections (bRTIs). METHODS A multicenter, retrospective cohort study that used the Pediatric Health Information System database between 2007 and 2014 of patients with tracheostomies aged ≤18 years with a primary diagnosis of bRTI (eg, tracheitis) or a primary diagnosis of a bRTI symptom (eg, cough) and a secondary diagnosis of bRTI. Primary outcomes were LOS and 30-day all-cause revisit rates. Secondary outcomes included hospital-level diagnostic testing and anti-Pseudomonas antibiotic use. We used mixed-effects negative binomial (for LOS) and logistic (for revisit) regression to explore the relationship between hospital-level diagnostic test utilization and the outcomes. RESULTS Data representing 4137 unique patients with a median age of 3 years (interquartile range: 1-9 years) were included. Median LOS was 4 days (interquartile range: 3-8 days), and the 30-day revisit rate was 24.9%. Use of diagnostic testing and empirical anti-Pseudomonas antibiotics varied significantly among hospitals (all P values <.001). After adjusting for patient and hospital characteristics, compared with low test utilization hospitals, there were no differences in 30-day all-cause revisit rates in moderate (adjusted odds ratio: 1.19; 95% confidence interval [CI]: 0.93-1.52) or high (adjusted odds ratio: 1.07; 95% CI: 0.82-1.39) utilization hospitals. LOS in hospitals with moderate (% difference: -0.8%; 95% CI: -14.4-14.9%) or high (% difference: 13.9%; 95% CI: -0.7-30.6%) test utilization was not significantly longer. CONCLUSIONS Given that care variations were not associated with outcomes, future research should focus on standardizing diagnosis and treatment of bRTIs and readmission prevention in this population.

Hot topics, urgent priorities, and ensuring success for racial/ethnic minority young investigators in academic pediatrics

BackgroundThe number of racial/ethnic minority children will exceed the number of white children in the USA by 2018. Although 38% of Americans are minorities, only 12% of pediatricians, 5% of medical-school faculty, and 3% of medical-school professors are minorities. Furthermore, only 5% of all R01 applications for National Institutes of Health grants are from African-American, Latino, and American Indian investigators. Prompted by the persistent lack of diversity in the pediatric and biomedical research workforces, the Academic Pediatric Association Research in Academic Pediatrics Initiative on Diversity (RAPID) was initiated in 2012. RAPID targets applicants who are members of an underrepresented minority group (URM), disabled, or from a socially, culturally, economically, or educationally disadvantaged background. The program, which consists of both a research project and career and leadership development activities, includes an annual career-development and leadership conference which is open to any resident, fellow, or junior faculty member from an URM, disabled, or disadvantaged background who is interested in a career in academic general pediatrics.MethodsAs part of the annual RAPID conference, a Hot Topic Session is held in which the young investigators spend several hours developing a list of hot topics on the most useful faculty and career-development issues. These hot topics are then posed in the form of six “burning questions” to the RAPID National Advisory Committee (comprised of accomplished, nationally recognized senior investigators who are seasoned mentors), the RAPID Director and Co-Director, and the keynote speaker.Results/conclusionsThe six compelling questions posed by the 10 young investigators—along with the responses of the senior conference leadership—provide a unique resource and “survival guide” for ensuring the academic success and optimal career development of young investigators in academic pediatrics from diverse backgrounds. A rich conversation ensued on the topics addressed, consisting of negotiating for protected research time, career trajectories as academic institutions move away from an emphasis on tenure-track positions, how “non-academic” products fit into career development, racism and discrimination in academic medicine and how to address them, coping with isolation as a minority faculty member, and how best to mentor the next generation of academic physicians.

Risk factors for hospitalizations due to bacterial respiratory tract infections after tracheotomy

Identify characteristics associated with hospital readmission due to bacterial respiratory tract infections (bRTI) after tracheotomy.

Length of Stay and Hospital Revisit After Bacterial Tracheostomy–Associated Respiratory Tract Infection Hospitalizations

OBJECTIVES To identify factors associated with longer length of stay (LOS) and higher 30-day hospital revisit rates for children hospitalized with bacterial tracheostomy-associated respiratory tract infections (bTARTIs). METHODS This was a multicenter, retrospective cohort study using administrative data from the Pediatric Health Information System database between 2007 and 2014 of patients 30 days to 17 years old with a principal discharge diagnosis of bTARTI or a principal discharge diagnosis of bTARTI symptoms with a secondary diagnosis of bTARTI. Primary outcomes of LOS (in days) and 30-day all-cause revisit rates (inpatient, observation, or emergency department visit) were analyzed by using a 3-level hierarchical regression model (discharges within patients within hospital). RESULTS We included 3715 unique patients and 7355 discharges. The median LOS was 4 days (interquartile range: 3-8 days), and the 30-day revisit rate was 30.5%. Compared with children 1 to 4 years old, children aged 30 days to 12 months had both longer LOS (adjusted length of stay [aLOS] = +0.9 days; 95% confidence interval [CI]: 0.6 to 1.3) and increased hospital revisit risk (adjusted odds ratio [aOR] = 1.5; 95% CI: 1.3 to 1.7). Other factors associated with longer LOS included public insurance (aLOS = +0.5 days; 95% CI: 0.2 to 0.8), 3 or more complex chronic conditions (CCCs), mechanical ventilation (acute or chronic), and empirical anti-Pseudomonas aeruginosa antibiotics (aLOS = +0.6 days; 95% CI: 0.3 to 0.9). Other factors associated with 30-day revisit included 4 or more CCCs (aOR = 1.3; 95% CI: 1.1 to 1.6) and chronic ventilator dependency (aOR = 1.1; 95% CI: 1.0 to 1.3). CONCLUSIONS Ventilator-dependent patients <12 months old with at least 4 CCCs are at highest risk for both longer LOS and 30-day revisit after discharge for bTARTIs. They may benefit from bTARTI prevention strategies and intensive care coordination while hospitalized.