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Background Pulmonary exacerbations (PEx) in people with cystic fibrosis (PwCF) are associated with significant morbidity. While standard PEx treatment for PwCF with Pseudomonas aeruginosa infection includes two IV antipseudomonal antibiotics, little evidence exists to recommend this approach. This study aimed to compare clinical outcomes of single versus double antipseudomonal antibiotic use for PEx treatment. Methods Retrospective cohort study using the linked CF Foundation Patient Registry-Pediatric Health Information System dataset. PwCF were included if hospitalized between 2007 and 2018 and 6–21 years of age. Regression modeling accounting for repeated measures was used to compare lung function outcomes between single versus double IV antipseudomonal antibiotic regimens using propensity-score weighting to adjust for relevant confounding factors. Results Among 10,660 PwCF in the dataset, we analyzed 2,578 PEx from 1,080 PwCF, of which 455 and 2,123 PEx were treated with 1 versus 2 IV antipseudomonal antibiotics, respectively. We identified no significant differences between PEx treated with 1 versus 2 IV antipseudomonal antibiotics either in change between pre- and post-PEx percent predicted forced expiratory volume in one second (ppFEV1) (–0.84%, [95% CI –2.25, 0.56]; P = 0.24), odds of returning to ≥90% of baseline ppFEV1 within 3 months following PEx (Odds Ratio 0.83, [95% CI 0.61, 1.13]; P = 0.24) or time to next PEx requiring IV antibiotics (Hazard Ratio 1.04, [95% CI 0.87, 1.24]; P = 0.69). Conclusions Use of 2 IV antipseudomonal antibiotics for PEx treatment in young PwCF was not associated with greater improvements in measured respiratory and clinical outcomes compared to treatment with 1 IV antipseudomonal antibiotic.

Background. Pseudomonas aeruginosa is a key respiratory pathogen in people with cystic fibrosis (CF). Due to its association with lung disease progression, initial detection of P. aeruginosa in CF respiratory cultures usually results in antibiotic treatment with the goal of eradication. Pseudomonas aeruginosa exhibits many different phenotypes in vitro that could serve as useful prognostic markers, but the relative relationships between these phenotypes and failure to eradicate P. aeruginosa have not been well characterized. Methods. We measured 22 easily assayed in vitro phenotypes among the baseline P. aeruginosa isolates collected from 194 participants in the 18-month EPIC clinical trial, which assessed outcomes after antibiotic eradication therapy for newly identified P. aeruginosa. We then evaluated the associations between these baseline isolate phenotypes and subsequent outcomes during the trial, including failure to eradicate after antipseudomonal therapy, emergence of mucoidy, and occurrence of an exacerbation. Results. Baseline P. aeruginosa isolates frequently exhibited phenotypes thought to represent chronic adaptation, including mucoidy. Wrinkly colony surface and irregular colony edges were both associated with increased risk of eradication failure (hazard ratios [95% confidence intervals], 1.99 [1.03–3.83] and 2.14 [1.32–3.47], respectively). Phenotypes reflecting defective quorum sensing were significantly associated with subsequent mucoidy, but no phenotype was significantly associated with subsequent exacerbations during the trial. Conclusions. Pseudomonas aeruginosa phenotypes commonly considered to reflect chronic adaptation were observed frequently among isolates at early detection. We found that 2 easily assayed colony phenotypes were associated with failure to eradicate after antipseudomonal therapy, both of which have been previously associated with altered biofilm formation and defective quorum sensing.

Lung disease associated with chronic airway infection is the main determinant of longevity and morbidity in people with cystic fibrosis (CF) [1]. Staphylococcus aureus is the bacterium cultured most commonly from the respiratory tracts of children with CF [2], and the earliest descriptions of CF lung infections focused on this species [3]. Subsequently, Pseudomonas aeruginosa was increasingly isolated from children with CF, and studies established an association between P. aeruginosa and CF lung disease [4, 5], largely shifting the focus of CF microbiological research and therapy. Recently, increases in S. aureus prevalence, both methicillin susceptible and methicillin resistant (MRSA), have been described in CF [6]. Recent studies of children with CF noted similar inflammation and lung function decline during infection with S. aureus compared with P. aeruginosa [7–9]. These observations have led to a reexamination of S. aureus and its role in CF lung disease [10]. Phenotypic variants of S. aureus called small-colony variants (SCVs) emerge during many chronic infections [11], including in CF [12–17]. Staphylococcus aureus SCVs grow slowly on most laboratory media due to metabolic defects, which also confer resistance to many antibiotics [11]. Staphylococcus aureus SCVs can be selected in vitro either by long-term exposure to specific antibiotics [11, 18] or growth with P. aeruginosa [19, 20], both of which occur commonly in CF airways. However, these various conditions select for phenotypically different SCVs, with distinct metabolic defects and antibiotic resistance profiles. As a result of their slow growth, S. aureus SCVs are difficult to detect unless specifically looked for. Currently, most clinical laboratories do not use culture methods required to detect SCVs or to estimate their prevalence and clinical impact. Recent studies of adults and children with CF in Europe [12–16] reported S. aureus SCV prevalences of between 8% [16] and 33% [13] and unadjusted associations with lower lung function [14, 15], but for several reasons those results cannot necessarily be extrapolated to other CF populations. For example, US and European CF centers differ substantially both in antibiotic treatment and prophylaxis practices [1, 2, 21, 22] and in rates of P. aeruginosa culture positivity [2, 6, 14, 22], 2 factors predicted to influence S. aureus SCV prevalence and antibiotic resistances. Children with CF also differ from adults in those 2 factors. We hypothesized that S. aureus SCVs would be common in US pediatric CF patients, but with different predicted antibiotic resistances from those found in previous (European) studies, warranting routine surveillance. To test these hypotheses, we performed a 2-year study of our hospital's CF population using specialized culture methods and detailed logs of antibiotic use. We focused on children due to their relatively mild disease, high rates of S. aureus, relatively little antibiotic exposure, and less frequent P. aeruginosa infection compared with adults, strengthening our ability to determine associations with specific selection pressures and disease severity.