Five-Year Community Surveillance Study for Acute Respiratory Infections Using Text Messaging: Findings From the MoSAIC Study.

BACKGROUND: Acute respiratory infections (ARI) are the most common infectious diseases globally. Community surveillance may provide a more comprehensive picture of disease burden than medically attended illness alone. METHODS: In this longitudinal study conducted from 2012 to 2017 in the Washington Heights/Inwood area of New York City, we enrolled 405 households with 1915 individuals. Households were sent research text messages twice weekly inquiring about ARI symptoms. Research staff confirmed symptoms by follow-up call. If ≥2 criteria for ARI were met (fever/feverish, cough, congestion, pharyngitis, myalgias), staff obtained a mid-turbinate nasal swab in participants' homes. Swabs were tested using the FilmArray reverse transcription polymerase chain reaction (RT-PCR) respiratory panel. RESULTS: Among participants, 43.9% were children, and 12.8% had a chronic respiratory condition. During the 5 years, 114 724 text messages were sent; the average response rate was 78.8% ± 6.8%. Swabs were collected for 91.4% (2756/3016) of confirmed ARI; 58.7% had a pathogen detected. Rhino/enteroviruses (51.9%), human coronaviruses (13.9%), and influenza (13.2%) were most commonly detected. The overall incidence was 0.62 ARI/person-year, highest (1.73) in <2 year-olds and lowest (0.46) in 18-49 year-olds. Approximately one-fourth of those with ARI sought healthcare; percents differed by pathogen, demographic factors, and presence of a chronic respiratory condition. CONCLUSIONS: Text messaging is a novel method for community-based surveillance that could be used both seasonally as well as during outbreaks, epidemics and pandemics. The importance of community surveillance to accurately estimate disease burden is underscored by the findings of low rates of care-seeking that varied by demographic factors and pathogens.

Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017-2020.

BACKGROUND: Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. METHODS: Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017-2018, 2018-2019, and 2019-2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. RESULTS: Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group-specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18-49, 50-64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3-13, 4-7, and 4-33 times, respectively, the incidence in patients without these conditions. CONCLUSIONS: We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults.

Testing the effects of combining azithromycin with inhaled tobramycin for P. aeruginosa in cystic fibrosis: a randomised, controlled clinical trial.

RATIONALE: Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa. This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV1) and greater reduction in P. aeruginosa sputum in response to tobramycin. METHODS: A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection. RESULTS: Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: -0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043). CONCLUSIONS: Despite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin.

Potential opportunities and challenges for infection prevention and control for cystic fibrosis in the modern era.

PURPOSE OF REVIEW: We describe recent changes in care for people with cystic fibrosis (PwCF) that could impact infection prevention and control (IP&C) practices. RECENT FINDINGS: Current IP&C guidelines primarily aim to prevent acquisition and transmission of pathogens in PwCF utilizing evidence-based recommendations for healthcare settings. Currently, highly effective modulator therapy (HEMT) is dramatically improving the clinical manifestations of cystic fibrosis and reducing pulmonary exacerbations and hospitalizations. Thus, it is feasible that long-term, sustained improvements in pulmonary manifestations of cystic fibrosis could favorably alter cystic fibrosis microbiology. The COVID-19 pandemic increased the use of virtual care, enabling PwCF to spend less time in healthcare settings and potentially reduce the risk of acquiring cystic fibrosis pathogens. The increasing use of whole genome sequencing (WGS) shows great promise in elucidating sources of cystic fibrosis pathogens, shared strains, and epidemic strains and ultimately could allow the cystic fibrosis community to monitor the safety of changed IP&C practices, if deemed appropriate. Finally, given the nonhealthcare environmental reservoirs for cystic fibrosis pathogens, practical guidance can inform PwCF and their families about potential risks and mitigation strategies. SUMMARY: New developments in the treatment of PwCF, a shift toward virtual care delivery of care, and use of WGS could change future IP&C practices.

The Epidemiology of Respiratory Syncytial Virus in New York City during the Coronavirus Disease-2019 Pandemic Compared with Previous Years.

Fewer respiratory syncytial virus infections were observed in 2020-2021 with interseasonal resurgence. Children were more likely to have severe disease with less known risk factors in comparison with controls from 2018-2019. The overall codetection rates were similar, but with higher parainfluenza, rhinovirus/enterovirus, and lower influenza proportions compared with previous seasons.

COVID-19 Infection, Prevention, and Control Considerations in the Obstetric Environment.

Pregnancy increases the risk of severe illness due to coronavirus disease 2019 (COVID-19). Thus, prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in all obstetrical health care settings requires consistent implementation of multiple evidence-based practices and consideration of local epidemiology, local regulations for COVID-19, and guidance from the Centers for Disease Control and Prevention and Professional Societies. COVID-safe practices should be implemented for patients, visitors/support persons, and health care personnel and include screening, appropriate personal protective equipment, and transmission precautions. Vaccination of all health care personnel, pregnant people, and their support persons remains the best strategy to prevent COVID-19.

Perioperative Antibiotics and Other Factors Associated with Postcesarean Infections: A Case-Control Study.

OBJECTIVE: Our objective was to determine modifiable risk factors associated with surgical site infection (SSI) and postpartum endometritis. We hypothesized that inappropriate surgical antibiotic prophylaxis would be a risk factor for both types of infections. STUDY DESIGN: This was a single-center case-control study of SSI and endometritis after cesarean delivery over a 2-year period from 2016 to 2017. Cases were identified by International Classification of Diseases, 10th Revision diagnosis codes, infection control surveillance, and electronic medical records search and were subsequently confirmed by chart review. Three controls were randomly selected for each case from all cesareans ± 48 hours from case delivery. Demographic, pregnancy, and delivery characteristics were abstracted. Separate multivariable logistic regression models were used to assess factors associated with SSI and endometritis. Postpartum outcomes, including length of stay and readmission, were also compared. RESULTS: We identified 141 cases of SSI and endometritis with an overall postpartum infection rate of 4.0% among all cesarean deliveries. In adjusted analysis, factors associated with both SSI and endometritis were intrapartum delivery, classical or other (non-low-transverse) uterine incision, and blood transfusion. Factors associated with SSI only included inadequate antibiotic prophylaxis, public insurance, hypertensive disorder of pregnancy, and nonchlorhexidine abdominal preparation; factors only associated with endometritis included ß-lactam allergy, anticoagulation therapy, and chorioamnionitis. Among cases, 34% of those with SSI and 25% of those with endometritis did not receive adequate antibiotic prophylaxis, compared with 12.9 and 13.5% in control groups, respectively. Failure to receive appropriate antibiotic prophylaxis was associated with an increased risk of SSI (adjusted odds ratio [aOR]: 4.4, 95% confidence interval [CI]: 1.3-15.6) but not endometritis (aOR 0.9, 95% CI 0.4-2.0). CONCLUSION: Inadequate surgical antibiotic prophylaxis was associated with an increased risk of SSI but not postpartum endometritis, highlighting the different mechanisms of these infections and the importance of prioritizing adequate surgical prophylaxis. Additional potentially modifiable factors which emerged included blood transfusion and chlorhexidine skin preparation. KEY POINTS: · Inadequate antibiotic prophylaxis is associated with a four-fold risk in surgical site infections.. · The most common cause for failure to achieve adequate surgical prophylaxis was inappropriate timing of antibiotics at or after skin incision.. · Blood transfusions are strongly associated (>10-fold risk) with both SSI and endometritis..

Bacteremia in Adults Admitted from the Emergency Department with Laboratory-Confirmed Respiratory Syncytial Virus.

BACKGROUND: Collecting blood cultures from patients admitted from the emergency department (ED) with acute respiratory infection (ARI) is common, but the rate of secondary bacteremia in adult patients admitted from the ED with ARI associated with respiratory syncytial virus (RSV) is unknown. Indiscriminate collection of blood cultures can be associated with contaminated blood cultures and increased inappropriate antimicrobial use and health care costs. OBJECTIVE: This study sought to determine the rate and etiology of secondary bacteremia, factors associated with secondary bacteremia, and factors associated with collecting blood cultures in the ED, in adults hospitalized with RSV. METHODS: We performed a retrospective substudy using data from a prospective study of adults admitted with RSV infections during two respiratory seasons (October 2017 to April 2018 and October 2018 to April 2019). Blood cultures were collected at the discretion of ED providers. We compared demographic and clinical characteristics among those with and without secondary bacteremia and among those with and without blood cultures collected using multivariate logistic regression models. RESULTS: Of the 365 hospitalized RSV-positive patients (mean age 68.8 years), 269 (73.7%) had blood cultures collected in the ED and 18 (6.7%) patients had secondary bacteremia, most commonly from a nonrespiratory source (n = 13). Patients with asthma and chronic obstructive pulmonary disease were significantly less likely to have secondary bacteremia. Patients who were immunocompromised, met systemic inflammatory response syndrome criteria, or had pneumonia described on chest x-ray reports were more likely to have blood cultures collected. CONCLUSIONS: Overall, 6.7% of adults hospitalized with RSV infections had secondary bacteremia, more commonly from nonrespiratory sources.

Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation.

The approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect the susceptibility profiles of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients. This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic P. aeruginosa infection. Sputum cultures were collected annually (2011 to 2016). The primary study endpoint was the proportion of subjects whose least susceptible P. aeruginosa isolate had an aztreonam MIC that was >8 µg/ml (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and percent of predicted forced expiratory volume in 1 s (FEV1% predicted) were obtained from the CF Foundation Patient Registry and compared between subjects meeting and those not meeting the primary endpoint. A total of 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13 to 22%) met the primary endpoint each year, and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual declines in lung function were comparable for subjects meeting and those not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it. The aztreonam susceptibility of P. aeruginosa remained consistent during the 5-year study. The relationship between P. aeruginosa isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with an accelerated decline in lung function but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01375036.).

High Prevalence of Gram-Negative Rod and Multi-Organism Surgical Site Infections after Pediatric Complex Tethered Spinal Cord Surgery: Preliminary Report from a Single-Center Study.

BACKGROUND: Surgical site infections (SSIs) are one of the most common complications following pediatric complex tethered spinal cord release. This patient population is similar in some ways to the neuromuscular scoliosis population, in which higher-than-expected rates of gram-negative SSIs have been identified. METHODS: We conducted a single-center retrospective chart review of all patients who underwent complex tethered spinal cord release over a 10-year period between 2007 and 2017. RESULTS: A total of 69 patients were identified, with 10 documented SSIs (14%). 50% of the SSIs were polymicrobial or included at least 1 gram-negative organism. Among the organisms isolated, 3 were fully or -partially resistant to cefazolin, the most common antibiotic prophylaxis in this population. CONCLUSION: Among children undergoing complex tethered spinal cord release, gram-negative and polymicrobial infections are a significant cause of SSIs. Although further multicenter data are needed, these findings suggest that standard antibiotic prophylaxis with cefazolin may not be sufficient.

A Multidisciplinary Approach to Pretransplant and Posttransplant Management of Cystic Fibrosis-Associated Liver Disease.

Approximately 5%-10% of patients with cystic fibrosis (CF) will develop advanced liver disease with portal hypertension, representing the third leading cause of death among patients with CF. Cystic fibrosis with advanced liver disease and portal hypertension (CFLD) represents the most significant risk to patient mortality, second only to pulmonary or lung transplant complications in patients with CF. Currently, there is no medical therapy to treat or reverse CFLD. Liver transplantation (LT) in patients with CFLD with portal hypertension confers a significant survival advantage over those who do not receive LT, although the timing in which to optimize this benefit is unclear. Despite the value and efficacy of LT in selected patients with CFLD, established clinical criteria outlining indications and timing for LT as well as disease-specific transplant considerations are notably absent. The goal of this comprehensive and multidisciplinary report is to present recommendations on the unique CF-specific pre- and post-LT management issues clinicians should consider and will face.

Decision-Making Around Positive Tracheal Aspirate Cultures: The Role of Neutrophil Semiquantification in Antibiotic Prescribing.

OBJECTIVES: Ventilator-associated infections are a major contributor to antibiotic use in the PICU. Quantitative or semiquantitative assessment of neutrophils (microscopic purulence) is routinely reported in positive cultures from tracheal aspirates. The role of microscopic purulence in guiding antibiotic therapy or its association with symptoms of ventilator-associated infections is less described in children. We examine microscopic purulence as an independent predictor of antibiotic use for positive tracheal aspirate cultures in the PICU. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. PATIENTS: Children admitted to the PICU, neuro-PICU, or cardiac PICU with a positive tracheal aspirate culture from January 1, 2016, to December 31, 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Positive tracheal aspirate cultures were reviewed. The outcome variable was antibiotic treatment that targeted the positive tracheal aspirate culture. The predictor variable was microscopic purulence, defined as moderate or many neutrophils on Gram stain report. Competing predictors included demographics, comorbidities, vital signs changes, respiratory support, and laboratory values. Of 361 positive cultures in the cohort, 81 (22%) were treated with antibiotics. Positive cultures with microscopic purulence were targeted for therapy more frequently (30% vs 11%). Microscopic purulence was the strongest predictor for antibiotic therapy (odds ratio, 3.3; 95% CI, 1.6-6.8) compared with fever (odds ratio, 2.0; 95% CI, 1.0-4.1) or increased respiratory support (odds ratio, 2.3; 95% CI, 1.2-4.3). There was no significant variation in symptomatology between microscopic purulence reported as moderate or many versus other (e.g., fever -24% vs 22%, increased respiratory support -36% vs 28%). Microscopic purulence was less prevalent with longer ventilator durations at the time of sampling. CONCLUSIONS: Microscopic purulence was an independent predictor of antibiotic therapy for positive tracheal aspirate cultures in our PICUs. However, microscopic purulence was not associated with clinical symptomatology.

Behavioral Interventions to Reduce Infections in Pediatric Long-term Care Facilities: The Keep It Clean for Kids Trial.

Children in pediatric long-term care facilities (pLTCF) represent a highly vulnerable population and infectious outbreaks occur frequently, resulting in significant morbidity, mortality, and resource use. The purpose of this quasi-experimental trial using time series analysis was to assess the impact of a 4-year theoretically based behavioral intervention on infection prevention practices and clinical outcomes in three pLTCF (288 beds) in New York metropolitan area including 720 residents, ages 1 day to 26 years with mean lengths of stay: 7.9-33.6 months. The 5-pronged behavioral intervention included explicit leadership commitment, active staff participation, work flow assessments, training staff in the World Health Organization "'five moments of hand hygiene (HH)," and electronic monitoring and feedback of HH frequency. Major outcomes were HH frequency, rates of infections, number of hospitalizations associated with infections, and outbreaks. Mean infection rates/1000 patient days ranged from 4.1-10.4 pre-intervention and 2.9-10.0 post-intervention. Mean hospitalizations/1000 patient days ranged from 2.3-9.7 before and 6.4-9.8 after intervention. Number of outbreaks/1000 patient days per study site ranged from 9-24 pre- and 9-18 post-intervention (total = 95); number of cases/outbreak ranged from 97-324 (total cases pre-intervention = 591 and post-intervention = 401). Post-intervention, statistically significant increases in HH trends occurred in one of three sites, reductions in infections in two sites, fewer hospitalizations in all sites, and significant but varied changes in the numbers of outbreaks and cases/outbreak. Modest but inconsistent improvements occurred in clinically relevant outcomes. Sustainable improvements in infection prevention in pLTCF will require culture change; increased staff involvement; explicit administrative support; and meaningful, timely behavioral feedback.

Surgical Site Infections following Spine Surgery for Non-idiopathic Scoliosis.

BACKGROUND: Surgical site infections (SSIs) following spine surgery in children and adolescents with nonidiopathic scoliosis are associated with increased morbidity and health care costs. Potentially modifiable risk factors for SSIs merit additional study in this population. METHODS: A single-center, retrospective cohort study was performed from August 2008 through December 2013 in children and adolescents undergoing surgery for nonidiopathic scoliosis to determine the trends in SSI rate and causative microorganisms. A standardized perioperative antimicrobial prophylaxis regimen was developed from September-October 2008. Potential risk factors for SSIs were assessed by multivariable analysis using Poisson regression models. Fusion procedures and growing construct procedures were analyzed separately. RESULTS: In all, 268 patients underwent 536 surgical procedures of whom 192 underwent 228 fusion procedures, 89 underwent 308 growing construct procedures, and 13 underwent both procedures during the study period. Twenty-one SSIs (3.9% of surgical procedures and 7.8% of patients) occurred within 90 days of surgery, 17 SSIs occurred after fusion procedures (4.5% of procedures and 8.9% of patients), and 4 SSIs occurred after growing construct procedures (1.3% of procedures and 4.5% of patients). There were 9 polymicrobial SSIs (42.9%). Of the 31 bacterial pathogens isolated, 48% were Gram-negative organisms. Among patients undergoing fusion procedures, SSIs were associated with underdosing of preoperative cefazolin [relative risk (RR)=4.99; 95% confidence interval (CI), 1.89-17.43; P=0.012] and tobramycin (RR=5.86; 95% CI, 1.90-18.06; P=0.002), underdosing of intraoperative (RR=5.65; 95% CI, 2.13-14.97; P=0.001) and postoperative (RR=3.86; 95% CI, 1.20-12.40; P=0.023) tobramycin, and any preoperative or intraoperative underdosing (RR=4.89; 95% CI, 1.70-14.12; P=0.003), after adjustment for duration of surgery. No factors were associated with SSIs in those undergoing growing construct procedures. During the study period, the SSIs rate declined (P<0.0001). CONCLUSIONS: Underdosing of tobramycin and preoperative cefazolin were associated with an increased SSI risk among patients undergoing fusion procedures. Future multicenter studies should further investigate the generalizability of these findings. LEVEL OF EVIDENCE: Level II-retrospective study.

National Testing of the Nursing-Kids Intensity of Care Survey for Pediatric Long-term Care.

PURPOSE: The purpose of this study is to test the Nursing-Kids Intensity of Care, a measure of the intensity of nursing care needs, defined as the quantity and type of direct and indirect care activities performed by caregivers in a national sample. DESIGN AND METHODS: A 40-item tool previously tested in a small sample was psychometrically tested on a sample of 116 children with complex medical conditions by 33 nurse raters across 11 pediatric sites. RESULTS: The Nursing-Kids Intensity of Care tool demonstrated components of usability, feasibility, inter-rater, test-retest and internal consistency reliability and construct validity in the national study sample. CONCLUSIONS: Additional testing to further establish psychometric sufficiency and expanded use to quantify the intensity of nursing care needs of children with complex medical conditions in pediatric long-term care settings is recommended. PRACTICE IMPLICATIONS: This novel measure could assist the nursing administrators, educators and staff of pediatric long-term care facilities assess the intensity of care needs of their residents.

Influenza Vaccine Effectiveness in a Low-Income, Urban Community Cohort.

In this community-based cohort study of 275 primarily low-income, urban households in New York City, overall 2013-2014 influenza vaccine effectiveness (VE) was 62.5% (95% confidence interval, 21.7%-82.0%). VE point estimates were highest against 2009 H1N1 and for those who were vaccinated in 2013-2014 but not in 2012-2013.

US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition.

US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease, such as cystic fibrosis (CF). Pulmonary disease (PD) caused by NTM has emerged as a major threat to the health of individuals with CF, but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition.

U.S. Ebola Treatment Center Clinical Laboratory Support.

Fifty-five hospitals in the United States have been designated Ebola treatment centers (ETCs) by their state and local health authorities. Designated ETCs must have appropriate plans to manage a patient with confirmed Ebola virus disease (EVD) for the full duration of illness and must have these plans assessed through a CDC site visit conducted by an interdisciplinary team of subject matter experts. This study determined the clinical laboratory capabilities of these ETCs. ETCs were electronically surveyed on clinical laboratory characteristics. Survey responses were returned from 47 ETCs (85%). Forty-one (87%) of the ETCs planned to provide some laboratory support (e.g., point-of-care [POC] testing) within the room of the isolated patient. Forty-four (94%) ETCs indicated that their hospital would also provide clinical laboratory support for patient care. Twenty-two (50%) of these ETC clinical laboratories had biosafety level 3 (BSL-3) containment. Of all respondents, 34 (72%) were supported by their jurisdictional public health laboratory (PHL), all of which had available BSL-3 laboratories. Overall, 40 of 44 (91%) ETCs reported BSL-3 laboratory support via their clinical laboratory and/or PHL. This survey provided a snapshot of the laboratory support for designated U.S. ETCs. ETCs have approached high-level isolation critical care with laboratory support in close proximity to the patient room and by distributing laboratory support among laboratory resources. Experts might review safety considerations for these laboratory testing/diagnostic activities that are novel in the context of biocontainment care.

Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis.

OBJECTIVES: Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children. METHODS: Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259. RESULTS: A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ±â€Š0.23 L/h/kg and 0.30 ±â€Š0.17 L/kg, respectively. Half-life was 1.11 ±â€Š0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home. CONCLUSIONS: In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule.