Development and Initial Characterization of Pigs with DNAI1 Mutations and Primary Ciliary Dyskinesia.

Mutations in more than 50 different genes cause primary ciliary dyskinesia (PCD) by disrupting the activity of motile cilia that facilitate mucociliary transport (MCT). Knowledge of PCD has come from studies identifying disease-causing mutations, characterizing structural cilia abnormalities, finding genotype-phenotype relationships, and studying the cell biology of cilia. Despite these important findings, we still lack effective treatments and people with PCD have significant pulmonary impairment. As with many other diseases, a better understanding of pathogenic mechanisms may lead to effective treatments. To pursue disease mechanisms, we used CRISPR-Cas9 to develop a PCD pig with a disrupted DNAI1 gene. PCD pig airway cilia lacked the outer dynein arm and had impaired beating. MCT was impaired under both baseline conditions and after cholinergic stimulation in PCD pigs. Neonatal PCD pigs developed neonatal respiratory distress with evidence of atelectasis, air trapping, and airway mucus obstruction. Despite airway mucus accumulation, lung bacterial counts were similar between neonatal wild-type and PCD pigs. Sinonasal disease was present in all neonatal PCD pigs. Older PCD pigs developed worsening airway mucus obstruction, inflammation, and bacterial infection. This pig model closely mimics the disease phenotype seen in people with PCD and can be used to better understand the pathophysiology of PCD airway disease.

Bioaerosols generated from toilet flushing in rooms of patients with Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is the most frequently reported hospital-acquired infection in the United States. Bioaerosols generated during toilet flushing are a possible mechanism for the spread of this pathogen in clinical settings. OBJECTIVE: To measure the bioaerosol concentration from toilets of patients with CDI before and after flushing. DESIGN: In this pilot study, bioaerosols were collected 0.15 m, 0.5 m, and 1.0 m from the rims of the toilets in the bathrooms of hospitalized patients with CDI. Inhibitory, selective media were used to detect C. difficile and other facultative anaerobes. Room air was collected continuously for 20 minutes with a bioaerosol sampler before and after toilet flushing. Wilcoxon rank-sum tests were used to assess the difference in bioaerosol production before and after flushing. SETTING: Rooms of patients with CDI at University of Iowa Hospitals and Clinics. RESULTS: Bacteria were positively cultured from 8 of 24 rooms (33%). In total, 72 preflush and 72 postflush samples were collected; 9 of the preflush samples (13%) and 19 of the postflush samples (26%) were culture positive for healthcare-associated bacteria. The predominant species cultured were Enterococcus faecalis, E. faecium, and C. difficile. Compared to the preflush samples, the postflush samples showed significant increases in the concentrations of the 2 large particle-size categories: 5.0 µm (P = .0095) and 10.0 µm (P = .0082). CONCLUSIONS: Bioaerosols produced by toilet flushing potentially contribute to hospital environmental contamination. Prevention measures (eg, toilet lids) should be evaluated as interventions to prevent toilet-associated environmental contamination in clinical settings.

Correlation between Broth Microdilution and Disk Diffusion Results when Testing Ceftazidime-Avibactam against a Challenge Collection of Enterobacterales Isolates: Results from a Multilaboratory Study.

We assessed the ceftazidime-avibactam disk diffusion breakpoints that provide the lowest discrepancy error rates by testing an Enterobacterales isolate collection with ceftazidime-avibactam MIC values near the breakpoints. Isolates (n = 112) were susceptibility tested by broth microdilution and disk diffusion methods in 3 laboratories. Current disk diffusion breakpoints (≥21/≤20 mm for susceptible/resistant) provided the lowest error rates, but confirmatory MIC testing is indicated for isolates with inhibition zones of 20 to 22 mm.

Sources of Staphylococcus aureus for patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: This study was designed to determine whether family members and health care workers are a source of Staphylococcus aureus for patients on peritoneal dialysis. DESIGN: Over 36 months, cultures were obtained from the nares of patients, family members that cared for the patients' catheters, and health care workers in a dialysis unit. Pulsed-field gel electrophoresis was performed on all S. aureus isolates. SETTING: A university-based peritoneal dialysis program. PARTICIPANTS: 74 patients, 32 family members, and 17 health care workers. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The number of patients that acquired S. aureus strains during the study period. RESULTS: Of the 48 patients whose initial nares cultures were negative, 7 (15%) acquired S. aureus strains. Overall, 24 of 53 (45%) patients that had 2 or more cultures obtained during the study gained strains. Potential sources were not identified for strains gained by 11 (46%) patients. Five patients appeared to acquire their strains from family members; however, other patients also shared related strains; 8 patients acquired strains shared by other patients. CONCLUSIONS: Family members and other patients appeared to be important sources of S. aureus for patients on peritoneal dialysis. Health care workers that carry S. aureus transiently may be important intermediaries. Good hand hygiene is essential to prevent transmission of S. aureus to these susceptible patients.