Antibiotic Treatment For Pulmonary Exacerbations Research Articles

A Three-year Longitudinal Assessment of Pseudomonas aeruginosa Antibiotic Susceptibility in Children With Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy

fibrosis is a genetic disease characterized by chronic lung infection, often with Pseudomonas aeruginosa, requiring repeated antibiotic treatment for pulmonary exacerbations. In the era of cystic fibrosis transmembrane conductance regulator modulator therapy, we assessed susceptibility to antipseudomonal antibiotics in modulator-eligible and modulator-ineligible children over 3 years and found that P. aeruginosa isolates largely remained susceptible to standard parenteral but not oral antimicrobial agents.

Health State Utilities Associated With Treatment Burden in Cystic Fibrosis: A Patient Valuation Study

BACKGROUNDWhile recent advancements in the treatment of cystic fibrosis (CF) have improved survival, reducing high levels of treatment burden remains a priority issue for many people with CF (pwCF). However, economic evaluations of novel interventions may fail to capture their impact on treatment burden due to a lack of suitable outcome measures. This study aimed to estimate health state utilities (HSUs), for changes in treatment burden associated with different CF treatments. RESEARCH QUESTIONWhat value do pwCF place on changes in treatment burden associated with intravenous antibiotic treatment of pulmonary exacerbations, inhaled medicines, and physiotherapy? STUDY DESIGNAND METHODS: Adults attending a specialist CF center were invited to participate in a web-based time trade-off interview. Participants valued their own health, and five health state vignettes describing varying levels of intensity of physiotherapy, inhaled, and IV antibiotic treatment. HSUs for additional instances of each treatment type were estimated using mixed effect linear regression models. RESULTSFifty one people with CF completed the interview (median age, 30 years; range, 19-66); 53% were female; mean FEV(1) % predicted, 65% [SD, 20%]).Mean utility scores for own health were very similar between the EQ-5D index value (0.81, SD 0.20) and the TTO value (0.82, SD 0.20), however limited concordance was observed at the individual level. Adjusted utility decrements associated with treatment burden were -0.037 (SE 0.008) for an additional annual IV antibiotic treatment, -0.029 (SE 0.014) for an additional daily physiotherapy session, and -0.019 (SE 0.013) for an additional daily inhaled medicine. INTERPRETATIONIncreasing treatment burden was associated with decreasing HSU values. The utility decrements associated with treatment burden changes suggest meaningful differences in health-related quality of life (HRQoL) for pwCF. These findings align with existing literature on the impact of treatment burden on HRQoL, and highlight the importance of considering treatment burden in economic evaluations of interventions in CF.

Factors associated with lung function response with oral antibiotic treatment of pulmonary exacerbations in cystic fibrosis

Pulmonary exacerbations treated with oral antibiotics (oPEx) have a significant effect on lung function decline in people with cystic fibrosis (CF). However, factors associated with lung function response with oPExs are not well defined.We performed a retrospective cohort study of pediatric and adult patients with CF followed in the Toronto CF Database. Lung function response was measured both as the change in forced expiratory volume in 1 second (FEV1) from Day 0 of antibiotic therapy to end of treatment as well as from baseline to end of treatment. Drop from baseline to Day 0 FEV1 was strongly associated with lung function response (p<0.001). Greater FEV1 improvements were associated with longer antibiotic treatment durations. Older, female patients had less improvements in FEV1 at end of treatment compared to younger, male patients.

Antibiotics and outcomes of CF pulmonary exacerbations in children infected with MRSA and Pseudomonas aeruginosa

Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone. Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting. 943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics. Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.

Changes in airway bacterial communities occur soon after initiation of antibiotic treatment of pulmonary exacerbations in cystic fibrosis

Chronic polymicrobial airway infections are a hallmark of cystic fibrosis (CF) lung disease. Antibiotic therapy is a primary treatment of CF pulmonary exacerbations (PEx); however, the impact of episodic antibiotic treatment on airway bacterial communities has not been well described. We analyzed sputum samples from adults with CF obtained immediately before and during antibiotic treatment of PEx. Sequencing of the V4 region of the bacterial 16S ribosomal RNA gene was used to assess changes in bacterial community structure during antibiotic treatment. The peak impact of antibiotic treatment was observed by day four or five of treatment. These findings advance our understanding of bacterial community dynamics during antibiotic treatment of PEx and complement recent and ongoing studies evaluating the optimal duration of antibiotic therapy for PEx.

Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis.

Stenotrophomonas maltophilia is one of the most common emerging multi-drug resistant organisms found in the lungs of people with cystic fibrosis and its prevalence is increasing. Chronic infection with Stenotrophomonas maltophilia has recently been shown to be an independent predictor of pulmonary exacerbation requiring hospitalization and antibiotics. However, the role of antibiotic treatment of Stenotrophomonas maltophilia infection in people with cystic fibrosis is still unclear. This is an update of a previously published review. The objective of our review is to assess the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. The primary objective is to assess this in relation to lung function and pulmonary exacerbations in the setting of acute pulmonary exacerbations. The secondary objective is to assess this in relation to the eradication of Stenotrophomonas maltophilia. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched a registry of ongoing trials and the reference lists of relevant articles and reviews. Date of latest search: 03 March 2020. Randomized controlled trials of Stenotrophomonas maltophilia mono-infection or Stenotrophomonas maltophilia co-infection with Pseudomonas aeruginosa in either the setting of an acute pulmonary exacerbation or a chronic infection treated with suppressive antibiotic therapy. Both authors independently assessed the trials identified by the search for potential inclusion in the review. We identified only one trial of antibiotic treatment of pulmonary exacerbations that included people with cystic fibrosis with Stenotrophomonas maltophilia. However, this trial had to be excluded because data was not available per pathogen. This review did not identify any evidence regarding the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. Until such evidence becomes available, clinicians need to use their clinical judgement as to whether or not to treat Stenotrophomonas maltophilia infection in people with cystic fibrosis. Randomized clinical trials are needed to address these unanswered clinical questions.

Parameters to Assess Response to Intra-Venous Antibiotic Treatment for Pulmonary Exacerbations in Cystic Fibrosis

Parameters to Assess Response to Intra-Venous Antibiotic Treatment for Pulmonary Exacerbations in Cystic Fibrosis

Decreased Fecal Calprotectin Levels in Cystic Fibrosis Patients After Antibiotic Treatment for Respiratory Exacerbation.

In all patients with cystic fibrosis (CF), gastrointestinal (GI) tract CF transmembrane conductance regulator dysfunction occurs early in life. The identical pathophysiological triad of obstruction, infection, and inflammation causes disease of the airways and in the intestinal tract (CF enteropathy). Mucus accumulation within GI tract is a niche for abnormal microbial colonization, leading to dysbiosis. Fecal calprotectin (FC) is a neutrophil cytosolic protein released during apoptosis and necrosis and reflects inflammatory status. Systemic antibiotic treatment for pulmonary exacerbations has been shown to improve systemic inflammatory markers and serum and sputum calprotectin. Antibiotic treatment aimed at pulmonary complaints may improve GI tract inflammatory status. We hypothesized that high levels of FC present during pulmonary exacerbation are due, in part, to multiorgan dysbiosis and thus should diminish with systemic antibiotic treatment. This prospective pilot study enrolled 14 patients with CF, with no current GI symptoms. FC levels and lung function were measured at the beginning and end of systemic antibiotic treatment. Compared to preantibiotic treatment baseline values, end of treatment FC levels declined significantly after antibiotic treatment, P = 0.004 and similarly, there was significant improvement in forced expiratory volume in 1 second, P = 0.002. High levels of FC during respiratory exacerbation may reflect a systemic exacerbation rather than solely pulmonary. Antibiotic treatment lowered the FC levels possibly by its impact on the intestinal microbiome.

Disadvantages of set length antibiotic treatment for pulmonary exacerbation

Disadvantages of set length antibiotic treatment for pulmonary exacerbation

Benefits of set length antibiotic treatment for pulmonary exacerbations

Benefits of set length antibiotic treatment for pulmonary exacerbations

WS16.1 Early multi-dimensional assessment of Parameters to assess Response to Intra-Venous Antibiotic Treatment for pulmonary Exacerbations: The PRIVATE Study

WS16.1 Early multi-dimensional assessment of Parameters to assess Response to Intra-Venous Antibiotic Treatment for pulmonary Exacerbations: The PRIVATE Study

Antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis.

Stenotrophomonas maltophilia is one of the most common emerging multi-drug resistant organisms found in the lungs of people with cystic fibrosis and its prevalence is increasing. Chronic infection with Stenotrophomonas maltophilia has recently been shown to be an independent predictor of pulmonary exacerbation requiring hospitalization and antibiotics. However, the role of antibiotic treatment of Stenotrophomonas maltophilia infection in people with cystic fibrosis is still unclear. This is an update of a previously published review. The objective of our review is to assess the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. The primary objective is to assess this in relation to lung function and pulmonary exacerbations in the setting of acute pulmonary exacerbations. The secondary objective is to assess this in relation to the eradication of Stenotrophomonas maltophilia. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of latest search: 27 May 2016. Any randomized controlled trial of Stenotrophomonas maltophilia mono-infection or Stenotrophomonas maltophilia co-infection with Pseudomonas aeruginosa in either the setting of an acute pulmonary exacerbation or a chronic infection treated with suppressive antibiotic therapy. Both authors independently assessed the trials identified by the search for potential inclusion in the review. The initial search strategy identified only one trial of antibiotic treatment of pulmonary exacerbations that included people with cystic fibrosis with Stenotrophomonas maltophilia. However, this trial had to be excluded because data was not available per pathogen. This review did not identify any evidence regarding the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. Until such evidence becomes available, clinicians need to use their clinical judgement as to whether or not to treat Stenotrophomonas maltophilia infection in people with cystic fibrosis. Randomized clinical trials are needed to address these unanswered clinical questions.

Probability of IV antibiotic retreatment within thirty days is associated with duration and location of IV antibiotic treatment for pulmonary exacerbation in cystic fibrosis

BackgroundThere are few objective data to guide management of cystic fibrosis (CF) pulmonary exacerbations. We studied intravenous (IV) antibiotic treatment failure as defined by a need to retreat patients with IV antibiotics within 30days of completion of a prior IV antibiotic treatment for pulmonary exacerbation. MethodsThe first IV-treated exacerbation on or after Jan. 1, 2010 among US CF Foundation Patient Registry patients was studied, combining treatments separated by <7days into single treatments. IV treatment duration categories were: 1–4, 5–8, 9–12, 13–16, 17–22, and ≥23days (inclusive). Logistic regressions for IV retreatment in ≤30days were adjusted with 12 categorical covariates, including age, sex, lung function, prior-year exacerbations, CF complications, CF Care Program, and ever/never treated in hospital. Results777 of 13,579 patients (5.7%) were retreated within 30days, with incidence varying by treatment duration: 1–4days, 8.7%; 5–8days; 6.6%; 9–12days, 3.2%; 13–16days, 4.5%; 17–22days, 6.2%; ≥23days, 10.3% and hospitalization: ever, 5.0%; never 8.5%. Adjusted odds ratios (OR) for retreatment (compared to 13–16days treatment) were: 1–4days, 1.94 [95%CI 1.49, 2.54] P<.001; 5–8days, 1.55 [1.18, 2.04] P=.002; 9–12days, 0.78 [0.58, 1.04] P=.09; 17–22days, 1.12 [0.88, 1.42] P=.37; ≥23days, 1.46 [1.12, 1.91] P=.005. Adjusted retreatment OR for never/ever hospitalized was 1.57 [1.29, 1.90] P<.001. Prior-year exacerbation number, oxygen therapy, non-invasive ventilation, and female sex were significantly associated with retreatment. Modeling hazard rate time-dependence showed that treatment duration and location-associated hazard rates attenuated within a few months after treatment. ConclusionAfter adjustment for covariates known to be associated with increased risk of IV treatment for exacerbation, IV antibiotic treatments of <9 and ≥23days and those without hospitalization were significant risk factors for IV retreatment within 30days of completion of an exacerbation treatment.

Factors associated with response to treatment of pulmonary exacerbations in cystic fibrosis patients

BackgroundPulmonary exacerbations are associated with significant lung function decline from baseline in cystic fibrosis (CF) and it is not well understood why some patients do not respond to antibiotic therapy. The objective of this study was to identify factors associated with lung function response to antibiotic treatment of pulmonary exacerbations. MethodsAs a secondary analysis of a randomized, controlled trial of intravenous antibiotic treatment for pulmonary exacerbations in CF patients, we investigated whether baseline factors and changes in sputum bacterial density, serum or sputum inflammatory markers were associated with recovery of lung function and risk of subsequent exacerbation. ResultsIn 36 of the 70 exacerbations (51%), patients’ lung function returned to >100% of their baseline at day 14 of antibiotic treatment; 34 exacerbations were classified as non-responders. Baseline characteristics were not significantly different between responders and non-responders. Less of a drop in FEV1 from baseline to exacerbation (OR 1.09, 95% CI 1.0, 1.18, p=0.04) as well as a greater decrease in sputum neutrophil elastase (OR 2.94, 95% CI 1.07, 8.06, p=0.04) were associated with response to antibiotic treatment at day 14. In addition, higher CRP (HR 1.35 (95% CI: 1.01, 1.78), p=0.04) and sputum neutrophil elastase (HR 1.71 (95% CI: 1.02, 2.88), p=0.04) at day 14 of antibiotic therapy were associated with an increased risk of subsequent exacerbation. ConclusionsInadequate reduction of inflammation during an exacerbation is associated with failure to recover lung function and increased risk of subsequent re-exacerbation in CF patients.

Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients

This study aimed to determine whether antimicrobial susceptibility testing of Pseudomonas aeruginosa grown as a biofilm, rather than planktonically, improves efficacy of antibiotic treatment for pulmonary exacerbations. This was a multicenter randomized, double-blind controlled trial of 14days of intravenous antibiotic treatment for pulmonary exacerbations chosen based on conventional vs. biofilm antimicrobial susceptibility results in CF patients with chronic P. aeruginosa infection. There were 74 exacerbations in 39 patients. A total of 46% (12/26) exacerbations in the conventional group compared to 40% (19/48) exacerbations in the biofilm group achieved a ≥3 log drop in P. aeruginosa sputum density (difference −0.03, 95% CI −0.5 to 0.4, p=0.9). Lung function improvements were similar in both groups. Biofilm antimicrobial susceptibility testing did not lead to improved microbiological or clinical outcomes compared to conventional methods in the treatment of pulmonary exacerbations in CF patients with chronic P. aeruginosa.

Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis

BackgroundA diverse array of bacterial species is present in the CF airways, in addition to those recognised as clinically important. Here, we investigated the relative impact of antibiotics, used predominantly to target Pseudomonas aeruginosa during acute exacerbations, on other non-pseudomonal species. MethodsThe relative abundance of viable P. aeruginosa and non-pseudomonal species was determined in sputa from 12 adult CF subjects 21, 14, and 7days prior to antibiotics, day 3 of treatment, the final day of treatment, and 10–14days afterwards, by T-RFLP profiling. ResultsOverall, relative P. aeruginosa abundance increased during antibiotic therapy compared to other bacterial species; mean abundance pre-antibiotic 51.0±36.0% increasing to 71.3±30.4% during antibiotic (ANOVA: F1,54=5.16; P<0.027). Further, the number of non-pseudomonal species detected fell; pre-antibiotic 6.0±3.3 decreasing to 3.7±3.3 during treatment (ANOVA: F1,66=5.11; P<0.027). ConclusionsAntibiotic treatment directed at P. aeruginosa has an additional significant impact on non-pseudomonal, co-colonising species.

Socioeconomic Status and the Likelihood of Antibiotic Treatment for Signs and Symptoms of Pulmonary Exacerbation in Children with Cystic Fibrosis

To determine whether socioeconomic status (SES) influences the likelihood of antibiotic treatment of pulmonary exacerbations in patients with cystic fibrosis (CF). We used data on 9895 patients ≤ 18 years old from the Epidemiologic Study of CF. After establishing an individual baseline of clinical signs and symptoms, we ascertained whether antibiotics were prescribed when new signs/symptoms suggested a pulmonary exacerbation, adjusting for sex, presence of Pseudomonas aeruginosa, the number of new signs/symptoms, and baseline disease severity. In a 12-month period, 20.0% of patients <6 years of age, 33.8% of patients 6 to 12 years of age, and 41.4% of patients 13 to 18 years of age were treated with any (oral, intravenous (IV), or inhaled) antibiotics; the percentage receiving IV antibiotics was 7.3%, 15.2%, and 20.9%, respectively. SES had little effect on treatment for pulmonary exacerbation with any antibiotics, but IV antibiotics were prescribed more frequently for patients with lower SES. SES-related disparities in CF health outcomes do not appear to be explained by differential treatment of pulmonary exacerbations.

The size of the spleen by magnetic resonance imaging in patients with cystic fibrosis; with and without diabetes--a novel observational study

Magnetic resonance imaging (MRI) has been shown to be a useful tool to evaluate the volume of the pancreas. There is currently no information about the size of the spleen in cystic fibrosis (CF) patients. We investigated 51 adult volunteers: 28 pancreatic insufficient CF patients [13 with CF-related diabetes (CFRD) and 15 non-diabetic] and 23 male non-CF patients [12 with type 1 diabetes mellitus (T1DM) and 11 healthy control subjects]. Patients with known liver cirrhosis or portal hypertension were excluded. The size of the spleen was measured in all subjects by an investigator unaware of patients' clinical status. For comparison of spleen size in the four study groups only male CF patients were included. For CF patients, spleen size was compared with forced expiratory volume in 1 s (FEV(1)), body mass index (BMI), total number of days of intravenous (IV) antibiotic treatment for pulmonary exacerbations in year previous to study, levels of circulating white blood cells, glycosylated haemoglobin A1c (HbA1c), and exocrine function of the pancreas, as assessed by daily requirement of oral lipase. Amongst the four study groups, spleen size was greatest in the male non-diabetic CF patients (P = 0.01). For CF patients, spleen size was greater in male compared to female patients (P = 0.012). For patients with CFRD, there was an inverse correlation between the spleen size and HbA1c (r = -0.59, P = 0.04) and the daily intake of supplementary lipase (r = -0.63, P = 0.02). The size of the spleen in patients with CFRD, but not in CF patients without CFRD, inversely correlated with the days of IV antibiotic treatment received in the year previous to the study (r = -0.67, P = 0.012). There was no correlation between spleen size and BMI, FEV1 and white blood cell counts in any group. On MRI, the spleen size was greatest in male non-diabetic CF patients in comparison with other groups. The size of the spleen in CFRD patients was smaller when diabetes was poorly controlled, when exocrine pancreatic function was greatly impaired and in those with greater need for IV antibiotics in the year prior to the study.

Changes in Pediatric Health-Related Quality of Life in Cystic Fibrosis After IV Antibiotic Treatment for Pulmonary Exacerbations

Intravenous (IV) antibiotic therapy for pulmonary exacerbations (PE) has been shown to improve pulmonary functioning for patients with cystic fibrosis (CF); however, little is known about its effects on pediatric health-related quality of life (HRQOL). This prospective study assessed the impact of IV treatment of a PE on generic and CF-specific HRQOL for children and adolescents with CF. Participants included 52 children and adolescents with CF experiencing a PE (M (age) = 13.6 years; 54% males; M(FEV(1%)) predicted = 58.8%). HRQOL, pulmonary functioning, and body mass index were assessed before and after IV antibiotic treatment. Results of this prospective, observational study indicated significant improvements on CFQ-R Respiratory (M (change score) = 11.7; 95% CI = 6.3-17.1; p < .0001) and Weight (M (change score) = 15.9; 95% CI = 7.9-23.8; p < .0001) scales. The CF-specific measure was more sensitive to changes in HRQOL than the generic instrument. These data suggest that CF-specific HRQOL improves with treatment for a PE with IV antibiotics. The noted statistically and clinically significant changes in the CFQ-respiratory scale indicate that the measure may be beneficial to pulmonary health care teams.

Decreased systemic bioavailability of L-arginine in patients with cystic fibrosis

BackgroundL-arginine is the common substrate for nitric oxide synthases and arginases. Increased arginase levels in the blood of patients with cystic fibrosis may result in L-arginine deficiency and thereby contribute to low airway nitric oxide formation and impaired pulmonary function.MethodsPlasma amino acid and arginase levels were studied in ten patients with cystic fibrosis before and after 14 days of antibiotic treatment for pulmonary exacerbation. Patients were compared to ten healthy non-smoking controls.ResultsSystemic arginase levels measured by ELISA were significantly increased in cystic fibrosis with exacerbation compared to controls (17.3 ± 12.0 vs. 4.3 ± 3.4 ng/ml, p < 0.02). Arginase levels normalized with antibiotic treatment. Plasma L-arginine was significantly reduced before (p < 0.05) but not after treatment. In contrast, L-ornithine, proline, and glutamic acid, all downstream products of arginase activity, were normal before, but significantly increased after antibiotic therapy. Bioavailability of L-arginine was significantly reduced in cystic fibrosis before and after exacerbation (p < 0.05, respectively).ConclusionThese observations provide further evidence for a disturbed balance between the L-arginine metabolic pathways in cystic fibrosis.