Background Monitoring potential changes in the epidemiology of cystic fibrosis (CF) pathogens furthers our understanding of the potential impact of interventions. Methods We performed a retrospective ...analysis using data reported to the Cystic Fibrosis Foundation Patient Registry (CFFPR) from 2006 to 2012 to determine the annual percent changes in the prevalence and incidence of selected CF pathogens. Pathogens included Pseudomonas aeruginosa , methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), Haemophilus influenzae , Burkholderia cepacia complex, Stenotrophomonas maltophilia , and Achromobacter xylosoxidans . Changes in nontuberculous mycobacteria (NTM) prevalence were assessed from 2010 to 2012, when the CFFPR collected NTM species. Results In 2012, the pathogens of highest prevalence and incidence were MSSA and P aeruginosa , followed by MRSA. The prevalence of A xylosoxidans and B cepacia complex were relatively low. From 2006 to 2012, the annual percent change in overall (as well as in most age strata) prevalence and incidence significantly decreased for P aeruginosa and B cepacia complex, but significantly increased for MRSA. From 2010 to 2012, the annual percent change in overall prevalence of NTM and Mycobaterium avium complex increased. Conclusions The epidemiology of CF pathogens continues to change. The causes of these observations are most likely multifactorial and include improvements in clinical care and infection prevention and control. Data from this study will be useful to evaluate the impact of new therapies on CF microbiology.
Objective To assess whether multiplex polymerase chain reaction (mPCR) vs non-mPCR testing impacts the use of antibiotics, chest radiographs, and isolation precautions. Study design We ...retrospectively compared use of antibiotics, chest radiographs, and isolation precautions for patients <18 years old (excluding neonates) hospitalized at a tertiary referral center tested for respiratory pathogens in the emergency department or during the first 2 hospital days, during 2 periods: June 2010-June 2012 (non-mPCR group) vs October 2012-May 2014 (mPCR group). Results Subjects (n = 2430) in the mPCR group were older, had more complex chronic conditions, and were admitted to the pediatric intensive care unit more often compared with the non-mPCR (n = 2349) group. Subjects in the mPCR group had more positive tests (42.4% vs 14.4%, P < .01), received fewer days of antibiotics (4 vs 5 median antibiotic days, P < .01), fewer chest radiographs performed, (59% vs 78%, P < .01), and were placed in isolation longer (20 vs 0 median isolation-hours, P < .01) compared with the non-mPCR group. In multivariable regression, patients tested with mPCR were less likely to receive antibiotics for ≥2 days (OR 0.5, 95% CI 0.5-0.6), chest radiographs at admission (OR 0.4, 95% CI 0.3-0.4), and more likely to be in isolation for ≥2 days (OR 2.4, 95% CI 2.1-2.8) compared with the non-mPCR group. Conclusions Use of mPCR testing for respiratory viruses among hospitalized patients was significantly associated with decreased healthcare resource utilization, including decreased use of antibiotics and chest radiographs, and increased use of isolation precautions.
Background: Numerous improvements in diagnostic and therapeutic strategies for patients with cystic fibrosis (CF) have occurred during
the past 2 decades. We hypothesized that these changes could ...impact trends in respiratory microbiology.
Methods: Data from the Cystic Fibrosis Foundation Patient Registry were used to examine trends in the incidence and prevalence of
bacterial pathogens isolated from patients with CF in the United States from 1995 to 2005.
Results: The number of patients with CF in the patient registry increased from 19,735 in 1995 to 23,347 in 2005. During the study
period, the reported annual prevalence of Pseudomonas aeruginosa significantly declined from 60.4% in 1995 to 56.1% in 2005 (p < 0.001). The decline was most marked in children 6 to 10 years
old (48.2 to 36.1%) and adolescents 11 to 17 years old (68.9 to 55.5%). Both the incidence (21.7% in 1995 and 33.2% in 2005)
and prevalence (37.0% in 1995 and 52.4% in 2005) of methicillin-susceptible Staphylococcus aureus significantly increased and the age-specific prevalence was highest in patients 6 to 17 years old. The prevalence of methicillin-resistant
S aureus increased from 0.1% in 1995 to 17.2% in 2005 and from 2002 to 2005 was highest in adolescents 11 to 17 years old. Both the
prevalence and incidence of Burkholderia cepacia complex declined, while the prevalence of Haemophilus influenzae , Stenotrophomonas maltophilia , and Alcaligenes xylosoxidans increased.
Conclusions: Data from the patient registry suggest that the epidemiology of bacterial pathogens in patients with CF changed during the
study period. Future studies should continue to monitor changing trends and define the association between these trends and
care practices in CF.
The judicious use of antibiotics is an important means to limit the emergence of antibiotic-resistant organisms. Although specific guidelines for neonates are often lacking, antibiotic stewardship ...principles can be applied to the neonatal intensive care unit. Principles include accurately identifying patients who need antibiotic therapy, using local epidemiology to guide the selection of empiric therapy, avoiding agents with overlapping activity, adjusting antibiotics when culture results become available, monitoring for toxicity, and optimizing the dose, route, and duration of therapy. Neonatal intensive care units should develop interdisciplinary antimicrobial stewardship teams with the support of their institutions. Prescriber audit and feedback, as well as preauthorization and formulary restriction of selected antibiotics, are recommended antimicrobial stewardship interventions. Ancillary strategies include education and computerized decision support. Metrics to evaluate antimicrobial stewardship programs should include measurements of patient safety and quality, such as rates of adverse drug events, and appropriate dosing and timing of perioperative prophylaxis.
Currently, available single and dual‐combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies have favorably altered the life course of individuals with cystic ...fibrosis (CF) by decreasing morbidities and increasing survival. However, even with CFTR modulator use, questions and challenges remain to optimize the management of lung infections. This review (a) identifies these ongoing challenges and discusses the current understanding of the potential impact of CFTR modulator therapy on infections; (b) describes ongoing research to optimize detection, diagnosis, and treatment of CF microorganisms; and (c) discusses strategies to develop new anti‐infective therapies. The CF Foundation has launched the Infection Research Initiative to fund research that will improve our understanding of the complex microbial ecology within the CF lung, improve detection of CF pathogens, optimize current treatment, including long‐term chronic therapies, and develop new anti‐infective therapies. Ongoing clinical trials to determine the optimal duration of treatment of pulmonary exacerbations and to diagnose and treat nontuberculous mycobacteria represent clinical research paradigms that could be used to answer other complex treatment questions. The anti‐infective pipeline includes both existing anti‐infective and non‐anti‐infective agents, many of which are proposed to have unique mechanisms of action in CF. Future studies plan to evaluate short‐ and long‐term clinical effectiveness and impact on infections, of the next generation of CFTR modulator therapy, the highly effective triple‐combination therapy, for individuals with CF, homozygous or heterozygous for F508del.
Antimicrobial-resistant pathogens are of increasing concern in the neonatal intensive care unit population. A myriad of resistance mechanisms exist in microorganisms, and management can be complex ...because broad-spectrum antibiotics are increasingly needed. Control and prevention of antibiotic-resistant organisms (AROs) require an interdisciplinary team with continual surveillance. Judicious use of antibiotics; minimizing exposure to risk factors, when feasible; and effective hand hygiene are crucial interventions to reduce infection and transmission of AROs.
Little is known about the molecular epidemiology of Staphylococcus aureus in Chinese neonatal intensive care units (NICUs). We describe the molecular epidemiology of S. aureus isolated from neonates ...on admission to Beijing Children's Hospital.
From May 2015-March 2016, nasal swabs were obtained on admission from 536 neonates. Cultures were also obtained from body sites with suspected infections. S. aureus isolates were characterized by staphylococcal chromosomal cassette (SCCmec) type, staphylococcal protein A (spa) type, multilocus sequence type (MLST), sasX gene, antimicrobial susceptibility and cytotoxicity. Logistic regression assessed risk factors for colonization.
Overall, 92 (17%) infants were colonized with S. aureus and 20 (3.7%) were diagnosed with culture-positive S. aureus infection. Of the colonized infants, 70% (64/92) harbored methicillin-susceptible S. aureus (MSSA), 30% (28/92) harbored methicillin-resistant S. aureus (MRSA) while 70% (14/20) of infected infants were culture-positive for MRSA, 30% (6/20) were culture-positive for MSSA. Risk factors for colonization included female sex, age 7-28 days, higher birthweight (3270 IQR 2020-3655 grams) and vaginal delivery (p<0.05). The most common MRSA and MSSA clones were community-associated ST59-SCCmecIVa-t437 (60%) and ST188-t189 (15%), respectively. The sasX gene was not detected. Some MSSA isolates (16%) were penicillin-susceptible and some MRSA isolates (18%) were oxacillin-susceptible. MRSA and MSSA had similar cytotoxicity, but colonizing strains were less cytotoxic than strains associated with infections.
S. aureus colonization was common in infants admitted to our NICU and two community-associated clones predominated. Several non-modifiable risk factors for S. aureus colonization were identified. These results suggest that screening infants for S. aureus upon admission and targeting decolonization of high-risk infants and/or those colonized with high-risk clones could be useful to prevent transmission.
Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is of increasing concern. No standardized epidemiologic ...investigation tool has been published for healthcare-associated NTM outbreak investigations. This report describes the design of an ongoing observational study to standardize the approach to NTM outbreak investigation among pwCF.
This is a parallel multi-site study of pwCF within a single Center who have respiratory NTM isolates identified as being highly-similar. Participants have a history of positive airway cultures for NTM, receive care within a single Center, and have been identified as part of a possible outbreak based on genomic analysis of NTM isolates. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of a shared healthcare-associated encounter(s) among patients in a Center and identification of environmental isolates that are genetically highly-similar to respiratory isolates recovered from pwCF. Secondary endpoints include characterization of potential transmission modes and settings, as well as incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region.
We hypothesize that genetically highly-similar strains of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from environmental sources. This novel study design will establish a standardized, evidence-based epidemiologic investigation tool for healthcare-associated NTM outbreak investigation within CF Care Centers, will broaden the scope of independent outbreak investigations and demonstrate the frequency and nature of healthcare-associated NTM transmission in CF Care Centers nationwide. Furthermore, it will provide valuable insights into modeling risk factors associated with healthcare-associated NTM transmission and better inform future infection prevention and control guidelines. This study will systematically characterize clinically-relevant NTM isolates of CF healthcare environmental dust and water biofilms and set the stage to describe the most common environmental sources within the healthcare setting harboring clinically-relevant NTM isolates.
ClinicalTrials.gov NCT04024423. Date of registry July 18, 2019.
Background While the mechanism of action by which azithromycin exerts positive effects in patients with cystic fibrosis remains unclear, evidence suggests that azithromycin may act as an ...immunomodulatory agent. We examined changes in systemic inflammatory markers in a double-blind, randomized, controlled trial of oral azithromycin in patients 6-18 years of age with cystic fibrosis who were uninfected with Pseudomonas aeruginosa. Methods WBC counts and differential, serum myeloperoxidase (MPO), high-sensitivity C reactive protein (hsCRP), intracellular adhesion molecule 1, IL-6, calprotectin, serum amyloid A (SAA), and granulocyte colony-stimulating factor (G-CSF) were measured at baseline and after 28 and 168 days of treatment in patients receiving either oral azithromycin or placebo. Results Inflammatory markers were similar in both groups at baseline. HsCRP, MPO, SAA, calprotectin, and the absolute neutrophil count (ANC) significantly decreased from baseline to day 28 in the azithromycin group compared with the placebo group ( P < .05). This treatment effect was sustained at day 168 for ANC, calprotectin, and SAA ( P < .05). Changes in hsCRP, calprotectin, and SAA at day 28 were negatively correlated with changes in FEV1 (L) and FEV1 (% predicted), as well as both absolute and relative changes in weight ( P < .05). Except for weight (%), the associations remained significant for calprotectin; FEV1 (L) and weight (%) remained significantly correlated with the 168-day change in hsCRP. The 168-day change in ANC was significantly correlated with changes in lung function, but not in weight; the change in G-CSF was significantly correlated with the change in weight (%) only. Conclusions In patients not infected with P aeruginosa , oral azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment. Trial registry ClinicalTrials.gov ; No.: NCT00431964; URL: www.clinicaltrials.gov
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