Browsing by Author "Hoffman, Lucas R."

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    Antibiotic Regimen Changes during Cystic Fibrosis Pediatric Pulmonary Exacerbation Treatment
    (American Thoracic Society, 2023) Cogen, Jonathan D.; Sanders, Don B.; Slaven, James E.; Faino, Anna V.; Somayaji, Ranjani; Gibson, Ron L.; Hoffman, Lucas R.; Ren, Clement L.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Rationale/Objectives: Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized. Methods: This was a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry Pediatric Health Information System. PEx were included if they occurred in children with CF from 6 to 21 years old who had been treated with intravenous antibiotics between January 1, 2006, and December 31, 2018. PEx with lengths of stay <5 or >21 days or for which treatment was delivered in an intensive care unit were excluded. An antibiotic change was defined as the addition or subtraction of any intravenous antibiotic between Hospital Day 6 and the day before hospital discharge. Inverse probability of treatment weighting was used to adjust for disease severity and indication bias, which might influence a decision to change antibiotics. Results: In all, 4,099 children with CF contributed 18,745 PEx for analysis, of which 8,169 PEx (43.6%) included a change in intravenous antibiotics on or after Hospital Day 6. The mean change in pre- to post-treatment percent predicted forced expiratory volume in 1 second (ppFEV1) was 11.3 (standard error, 0.21) among events in which an intravenous antibiotic change occurred versus 12.2 (0.18) among PEx without an intravenous antibiotic change (P = 0.001). Similarly, the odds of return to ⩾90% of baseline ppFEV1 were less for PEx with antibiotic changes than for those without changes (odds ratio [OR], 0.89 [95% confidence interval (CI), 0.80–0.98]). The odds of returning to ⩾100% of baseline ppFEV1 did not differ between PEx with versus without antibiotic changes (OR, 0.94 [95% CI, 0.86–1.03]). In addition, PEx treated with intravenous antibiotic changes were associated with higher odds of future PEx (OR, 1.17 [95% CI, 1.12–1.22]). Conclusions: In this retrospective study, changing intravenous antibiotics during PEx treatment in children with CF was common and not associated with improved clinical outcomes.
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    Effects of Therapeutic Antibiotic Exposure on the Oropharyngeal and Fecal Microbiota in Infants With Cystic Fibrosis
    (Wiley, 2025) Hayden, Hillary S.; Nelson, Maria T.; Ross, Sydney E.; Verster, Adrian J.; Bouzek, Drake C.; Eng, Alex; Waalkes, Adam; Penewit, Kelsi; Kopp, Benjamin T.; Siracusa, Christopher; Rock, Michael J.; Salipante, Stephen J.; Hoffman, Lucas R.; Sanders, Don B.; Pediatrics, School of Medicine
    Background: Systemic antibiotics can impact all microbes inhabiting patients, regardless of the intended target organism(s). We studied the simultaneous effects on respiratory and fecal microbiomes of β-lactam antibiotics administered for respiratory symptoms in infants with cystic fibrosis (IWCF). Objective: To compare the magnitude and duration of intended (respiratory) and unintended (fecal) antimicrobial action by analyzing oropharyngeal (OP) and fecal microbiota in IWCF. Design: Shotgun metagenomic sequencing and qPCR were performed on OP and fecal samples collected longitudinally from 14 IWCF (ages 1-17 months) during ("On Antibiotics") and after ("Off Antibiotics") β-lactam therapy, and from 5 IWCF (3-16 months) never treated with antibiotics. Results: Total bacterial loads (TBL) for On Antibiotics samples were lower than for both Never (OP and fecal) and Off Antibiotics samples (fecal only). α-diversities (within-sample) for OP On Antibiotics samples were lower than for Never and Off Antibiotics samples but did not differ between fecal sample groups. β-diversity (between-sample) differed between all OP sample groups and between fecal On and Never Antibiotics and Off and Never antibiotics samples; however, fecal On and Off Antibiotics sample β-diversities did not differ. Patterns of change in antibiotic resistance gene abundances reflected shifts in microbial community composition. Conclusions: β-lactam antibiotic exposure was followed by marked alterations in both OP and fecal microbiota. While microbiota appeared to rebound after treatment in both sample types, our results suggest that fecal microbiota recovered less than OP. The clinical consequences of these findings should be studied in IWCF and other populations frequently treated with antibiotics.