Acute Pulmonary Exacerbations Research Articles

1635 Catch me if you can: a rare case of two-staged MitraClip detachment

Abstract Case report A 74-year-old man presented with acute heart failure and chronic obstructive pulmonary disease exacerbation. His medical history revealed: anterior myocardial infarction in 2005, treated with primary PCI of left anterior descending coronary artery followed by triple coronary artery bypass, atrial fibrillation, hypertension, diabetes mellitus and obesity. Transthoracic and transesophageal echocardiography (TEE) showed severe functional ischemic mitral regurgitation (MR) with multiple jets, the main one involving the A2-P2 scallops due to asymmetric tethering of the posterior leaflet. The vena contracta diameter (VC) was 8 mm, the effective regurgitant orifice area (EROA) 0.53 cm². Global left ventricular (LV) function was preserved with inferior-posterior wall akinesis. After "Heart Team" discussion, due to high surgical risk, the patient was referred for percutaneous mitral valve repair (PMVR) using MitraClip (MC) system (Abbott Vascular, Illinois). One clip (MC-XTR) was placed at the A3-P3 segments; subsequently, prior to releasing a second clip (MC-XTR), the first one partially detached from the posterior leaflet (Fig A). A third clip (MC-NTR) was implanted medially. The grasp was challenging but at the end of the procedure, the first clip appeared stable and marked reduction of MR was achieved (Fig B). 7 days later, the patient became symptomatic for resting dyspnea and worsened his clinical status. A control 2D-3D TEE revealed a complete detachment of the first implanted clip, visible distally into the LV, trapped in the mitral valve subchordal apparatus (Fig C). This resulted in massive MR (VC: 12 mm, EROA: 0.91 cm²) with an eccentric posteriorly directed regurgitant jet (Fig D). The patient underwent emergency surgical retrieval of the migrated clip, and removal of the torn mitral valve anterior leaflet. The other two clips were also removed (Fig E), and a bioprosthetic mitral valve was implanted. The procedure was completed uneventfully and the patient is in stable conditions at 2-months follow-up. Discussion The constant stretching and whip effect of the mitral leaflets captured between the clips arms, used in PMVR, can lead to complications. Partial clip detachment is a rare adverse event described in ∼0.7-4.9% of patients within 30 days after MC intervention*. We experienced a two-staged MC detachment that is an even rarer complication and requires emergency surgery. In addition, we highlights the usefulness of 3D TEE for early diagnosis and better imaging characterization in patients who develop complications after MC procedure. No conflict of interest. *Puls M, Lubos E, Boekstegers P, von Bardeleben RS, Ouarrak T, Butter C, Zuern CS, Bekeredjian R, Sievert H, Nickenig G, Eggebrecht H, Senges J, Schillinger W. One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from German transcatheter mitral valve interventions registry. Eur Heart J 2016;37:703-12. Abstract 1635 Figure.

The use of extracorporeal carbon dioxide removal in acute chronic obstructive pulmonary disease exacerbation: a narrative review.

Chronic obstructive pulmonary disease (COPD) exacerbation induces hypercapnic respiratory acidosis. Extracorporeal carbon dioxide removal (ECCO2R) aims to eliminate blood carbon dioxide (CO2) in order to reduce adverse effects from hypercapnia and the related acidosis. Hypercapnia has deleterious extra-pulmonary consequences in increasing intracranial pressure and inducing and/or worsening right heart failure. During COPD exacerbation, the use of ECCO2R may improve the efficacy of non-invasive ventilation (NIV) in terms of CO2 removal, decrease respiratory rate and reduce dynamic hyperinflation and intrinsic positive end expiratory pressure, which all contribute to increasing dead space. Moreover, ECCO2R may prevent NIV failure while facilitating the weaning of intubated patients from mechanical ventilation. In this review of the literature, the authors will present the current knowledge on the pathophysiology related to COPD, the principles of the ECCO2R technique and its role in acute and severe decompensation of COPD. However, despite technical advances, there are only case series in the literature and few prospective studies to clearly establish the role of ECCO2R in acute and severe COPD decompensation.

Comparison of Different Functional Capacity Tests in Cystic Fibrosis Patients With Acute Pulmonary Exacerbation

Comparison of Different Functional Capacity Tests in Cystic Fibrosis Patients With Acute Pulmonary Exacerbation

Multitarget CFTR Modulators Endowed with Multiple Beneficial Side Effects for Cystic Fibrosis Patients: Toward a Simplified Therapeutic Approach †.

Cystic fibrosis (CF) is a multiorgan disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR). In addition to respiratory impairment due to mucus accumulation, viruses and bacteria trigger acute pulmonary exacerbations, accelerating disease progression and mortality rate. Treatment complexity increases with patients' age, and simplifying the therapeutic regimen represents one of the key priorities in CF. We have recently reported the discovery of multitarget compounds able to "kill two birds with one stone" by targeting F508del-CFTR and PI4KIIIβ and thus acting simultaneously as CFTR correctors and broad-spectrum enterovirus (EV) inhibitors. Starting from these preliminary results, we report herein a hit-to-lead optimization and multidimensional structure-activity relationship (SAR) study that led to compound 23a. This compound showed good antiviral and F508del-CFTR correction potency, additivity/synergy with lumacaftor, and a promising in vitro absorption, distribution, metabolism, and excretion (ADME) profile. It was well tolerated in vivo with no sign of acute toxicity and histological alterations in key biodistribution organs.

Prevalence and factors associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis

BackgroundThe relation between malnutrition and pulmonary death in patients with cystic fibrosis (CF) has resulted in intensive nutritional intervention over the last few decades, leading to a significant decline in underweight and the emergence of overweight/obesity as a potential new problem. MethodsWe performed a cross-sectional database analysis of 484 adults with CF seen at the University of Minnesota CF Center between January 2015-January 2017, to determine the prevalence and pulmonary/cardiovascular risk factors associated with overweight and obesity in this population. ResultsMean age was 35.2 ± 11.6 years. 5.2% were underweight (BMI<18.5 kg/m2), 62.6% normal weight (BMI ≥ 18.5–24.9 kg/m2), 25.6% overweight (BMI ≥ 25–29.9 kg/m2) and 6.6% obese (BMI ≥ 30 kg/m2). In the subgroup with severe genotypes, 25% had BMI ≥ 25 kg/m2. In the entire cohort, overweight/obese were likely to be older (OR = 1.04, p < 0.0001) and to have a mild CFTR genotype (OR = 3.33, p = 0.0003) and modestly elevated triglyceride levels (OR = 1.008, p < 0.0001). The prevalence of hypertension was higher in overweight (25%) and obese (31%) than normal (17%) or underweight (16%), p = 0.01. Total cholesterol levels were higher in overweight/obese versus normal/underweight (144–147 vs 123–131 mg/dL, p = 0.04) as were LDL levels (70–71 vs 53–60 mg/dL, p = 0.02), but all were within the normal range. Percent predicted FEV1 was higher in overweight/obese (78–81%) versus underweight (59%) and normal (70%), p < 0.0001, and overweight/obese experienced significantly fewer acute pulmonary exacerbations. ConclusionsOverweight/obesity is common in adults with CF including those with severe genotypes. Lung function is better in the overweight/obese and lipid levels are within the normal range, albeit higher than in normal/underweight.

Acute Pulmonary Exacerbations in Cystic Fibrosis.

With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the disease course, prognosis, and complications. This work has now led to a number of large scale clinical trials with the goal of improving the treatment paradigm for CF pulmonary exacerbation. The primary goal of this review is to provide a summary of the pathophysiology, the clinical epidemiology, microbial epidemiology, outcome and the treatment of CF pulmonary exacerbation.

Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics.

The most common cause of death in cystic fibrosis (CF) patients is progressive lung function decline, which is punctuated by acute pulmonary exacerbations (APEs). A major challenge is to discover biomarkers for detecting an oncoming APE and allow for pre-emptive clinical interventions. Metabolic profiling of exhaled breath condensate (EBC) samples collected from CF patients before, during, and after APEs and under stable conditions (n = 210) was performed using ultraperformance liquid chromatography (UPLC) coupled to Orbitrap mass spectrometry (MS). Negative ion mode MS data showed that classification between metabolic profiles from "pre-APE" (pending APE before the CF patient had any signs of illness) and stable CF samples was possible with good sensitivities (85.7 and 89.5%), specificities (88.4 and 84.1%), and accuracies (87.7 and 85.7%) for pediatric and adult patients, respectively. Improved classification performance was achieved by combining positive with negative ion mode data. Discriminant metabolites included two potential biomarkers identified in a previous pilot study: lactic acid and 4-hydroxycyclohexylcarboxylic acid. Some of the discriminant metabolites had microbial origins, indicating a possible role of bacterial metabolism in APE progression. The results show promise for detecting an oncoming APE using EBC metabolites, thus permitting early intervention to abort such an event.

State of the art in cystic fibrosis pharmacology-Optimization of antimicrobials in the treatment of cystic fibrosis pulmonary exacerbations: I. Anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics.

Acutepulmonary exacerbations (APE) are a complication of cystic fibrosis (CF) and are associated with morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is one of many organisms that has been detected in the airways of patients with CF. This review provides an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-MRSA antibiotics (ie, ceftaroline, clindamycin, fluoroquinolone derivatives (ciprofloxacin, levofloxacin), glycopeptide derivatives (telavancin, vancomycin), linezolid, rifampin, sulfamethoxazole/trimethoprim (SMZ/TMP), and tetracycline derivatives (doxycycline, minocycline, tigecycline) in the treatment of APE and identifies areas where further study is warranted. A recent utilization study of antimicrobials for anti-MRSA has shown some CF Foundation accredited care centers and affiliate programs are using doses higher than the FDA-approved doses. Further studies are needed to determine the PK/PD properties in CF patients with clindamycin, minocycline, rifampin, SMZ/TMP, telavancin, and tigecycline; as well as, efficacy and tolerability studies with ciprofloxacin, clindamycin, doxycycline, levofloxacin, minocycline, rifampin, SMZ/TMP, in CF patients with MRSA.

Azithromycin during Acute Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization (BACE). A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial

Rationale: Azithromycin prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPDs); however, its value in the treatment of an AECOPD requiring hospitalization remains to be defined.Objectives: We investigated whether a 3-month intervention with low-dose azithromycin could decrease treatment failure (TF) when initiated at hospital admission and added to standard care.Methods: In an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, patients who had been hospitalized for an AECOPD and had a smoking history of ≥10 pack-years and one or more exacerbations in the previous year were randomized (1:1) within 48 hours of hospital admission to azithromycin or placebo. The study drug (500 mg/d for 3 d) was administered on top of a standardized acute treatment of systemic corticosteroids and antibiotics, and subsequently continued for 3 months (250 mg/2 d). The patients were followed for 6 months thereafter. Time-to-first-event analyses evaluated the TF rate within 3 months as a novel primary endpoint in the intention-to-treat population, with TF defined as the composite of treatment intensification with systemic corticosteroids and/or antibiotics, a step-up in hospital care or readmission for respiratory reasons, or all-cause mortality.Measurements and Main Results: A total of 301 patients were randomized to azithromycin (n = 147) or placebo (n = 154). The TF rate within 3 months was 49% in the azithromycin group and 60% in the placebo group (hazard ratio, 0.73; 95% confidence interval, 0.53-1.01; P = 0.0526). Treatment intensification, step-up in hospital care, and mortality rates within 3 months were 47% versus 60% (P = 0.0272), 13% versus 28% (P = 0.0024), and 2% versus 4% (P = 0.5075) in the azithromycin and placebo groups, respectively. Clinical benefits were lost 6 months after withdrawal.Conclusions: Three months of azithromycin for an infectious AECOPD requiring hospitalization may significantly reduce TF during the highest-risk period. Prolonged treatment seems to be necessary to maintain clinical benefits.

A pilot study on Short Physical Performance Battery in Geriatric Heart Failure: Prediction of adverse events at six months?

Aims: To evaluate the outcomes of heart failure in the elderly (60 years or older) by Short Physical Performance Battery scores at six months of discharge. Methods: One hundred elderly patients with heart failure were evaluated at discharge, at 3 and 6 months after discharge by Short Physical Performance Battery. Results: Of the 100 patients discharged from hospital, mean age was 65.13 ± 6.3 years, 65 percent were males, Heart failure with reduced ejection fraction was present in 77%, and 26 (26%) had died by six months. Readmissions were mainly due to acute decompensated heart failure or Chronic Obstructive Pulmonary Disease exacerbations. There was a good correlation between Short Physical Performance Battery and Ejection fraction. The Short Physical Performance Battery scores were low at discharge but improved over six months in those who were alive. All those who died at six months had a baseline Short Physical Performance Battery score of 6 or less. Conclusion: The Short Physical Performance Battery can identify heart failure patients at discharge who have a high risk of short term mortality. A multi-disciplinary intervention may be useful in improving outcomes.

The Effects of Respiratory Viruses on the Acute Pulmonary Exacerbations in Cystic Fibrosis Patients

The Effects of Respiratory Viruses on the Acute Pulmonary Exacerbations in Cystic Fibrosis Patients

Clinical Utility of the 1-minute Sit to Stand Test as a Measure of Submaximal Exercise Tolerance in Patients With Cystic Fibrosis During Acute Pulmonary Exacerbation

Clinical Utility of the 1-minute Sit to Stand Test as a Measure of Submaximal Exercise Tolerance in Patients With Cystic Fibrosis During Acute Pulmonary Exacerbation

Significance of Interstitial Lung Disease on Outcomes Following Cardiac Surgery

Interstitial lung disease (ILD) is a known risk factor for noncardiac surgery due to acute pulmonary exacerbations but its impact after cardiac surgery is not known. We examined perioperative outcomes and risk factors for long-term survival in ILD patients who underwent cardiac surgery. From January 2002 to June 2017, 294 cardiac surgery patients with a previous ILD diagnosis, including 75 patients with idiopathic pulmonary fibrosis (IPF), were identified. A comparison cohort of 1,481 non-ILD patients was selected based on a priori variables. Long-term survival was evaluated using Cox proportional hazard modeling. Median follow-up was 6.4 years. ILD patients had higher postoperative mortality, reintubation rates, longer intensive care unit stay, and higher 30-day readmission rates (all p <0.05). Kaplan-Meier estimates of survival at 1, 5, and 10 years were 89%, 62%, and 37% for the non-IPF ILD cohort, 89%, 50%, and 13% for the IPF cohort, and 95%, 82%, and 67% for the comparison cohort, respectively (overall p <0.001). These significant differences in survival persisted in our risk-adjusted survival analysis. Adjusted survival analysis identified IPF (hazard ratio 3.04) and ILD (non-IPF; hazard ratio 1.78) as significant contributors to all-cause mortality. However, there were no changes in pulmonary function tests after 48 months postprocedure. In conclusion, ILD patients who underwent cardiac surgery have increased operative mortality, reintubation rates, longer intensive care unit, and higher 30-day readmissions compared with non-ILD patients. Moreover, severity of ILD, especially in IPF, appears to be associated with shorter long-term survival. In these patients, pulmonary risk stratification and multidisciplinary team approach are crucial.

Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial

Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF. The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations. This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%). A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin. Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.

Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis

In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. Eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. Plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 16S rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. Therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration.

The renoprotective effect of concomitant fosfomycin in the treatment of pulmonary exacerbations in cystic fibrosis.

BackgroundFosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [N-acetyl-β-d-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and β2-microglobulin].Methods Using a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin).Results Urinary NAG (P = 0.003) and AAP (P = 0.03) following treatment with concomitant fosfomycin were lower than those after treatment with tobramycin and colomycin alone. Fosfomycin attenuated the total 24-h urinary protein leak (P = 0.0001). The 14-day improvements in all surrogate markers of exacerbation resolution (FEV1% predicted, FVC, white cell count and C-reactive protein) were similar for both treatment regimens.Conclusion The addition of fosfomycin reduces acute renal injury caused by IV aminoglycoside therapy in CF pulmonary exacerbations.

Microbiome networks and change-point analysis reveal key community changes associated with cystic fibrosis pulmonary exacerbations

Over 90% of cystic fibrosis (CF) patients die due to chronic lung infections leading to respiratory failure. The decline in CF lung function is greatly accelerated by intermittent and progressively severe acute pulmonary exacerbations (PEs). Despite their clinical impact, surprisingly few microbiological signals associated with PEs have been identified. Here we introduce an unsupervised, systems-oriented approach to identify key members of the microbiota. We used two CF sputum microbiome data sets that were longitudinally collected through periods spanning baseline health and PEs. Key taxa were defined based on three strategies: overall relative abundance, prevalence, and co-occurrence network interconnectedness. We measured the association between changes in the abundance of the key taxa and changes in patient clinical status over time via change-point detection, and found that taxa with the highest level of network interconnectedness tracked changes in patient health significantly better than taxa with the highest abundance or prevalence. We also cross-sectionally stratified all samples into the clinical states and identified key taxa associated with each state. We found that network interconnectedness most strongly delineated the taxa among clinical states, and that anaerobic bacteria were over-represented during PEs. Many of these anaerobes are oropharyngeal bacteria that have been previously isolated from the respiratory tract, and/or have been studied for their role in CF. The observed shift in community structure, and the association of anaerobic taxa and PEs lends further support to the growing consensus that anoxic conditions and the subsequent growth of anaerobic microbes are important predictors of PEs.

Amikacin target achievement in adult cystic fibrosis patients utilizing Monte Carlo simulation.

Pseudomonas aeruginosa (PsA) is a common pathogen in cystic fibrosis (CF). Management of an acute pulmonary exacerbation (APE) caused by PsA is dual anti-pseudomonal antibiotics, a beta-lactam plus aminoglycoside. Aminoglycoside dosing in CF differs from the general population due to altered pharmacokinetics. The primary objective of this study was to utilize pharmacokinetic data from adult CF patients that received amikacin to determine the probability of target attainment for APEs caused by PsA. This was a single-center, non-randomized, retrospective cohort study of patients >18 years with CF that received intravenous amikacin between January 2010 and July 2016. Amikacin dose, frequency, and serum concentrations were used to calculate pharmacokinetic parameters assuming a one-compartment model. Monte Carlo simulation was conducted with MIC values from CF patients with a PsA positive sputum culture between January 2014 and September 2016 to predict concentration-time profiles for different doses of amikacin. This study included pharmacokinetic parameters for 14 amikacin courses administered to six unique patients. The average empiric dose of amikacin was 24.3 ± 14.6 mg/kg, achieving a peak:MIC ratio ≥8 at a rate of 37% (median 5.87; IQR 3.05-10.96). A dose of 45 mg/kg/day was needed to achieve target peak:MIC ratios 90% of the time for a PsA MIC of 8 mg/L. Our data suggests it may not be clinically feasible to utilize amikacin for PsA isolates with a MIC of 16 mg/L. Current guideline dosing recommendations of amikacin 30-35 mg/kg/day are only adequate for PsA with a MIC ≤4 mg/L.

Machine Learning Algorithms Utilizing Functional Respiratory Imaging May Predict COPD Exacerbations

Acute chronic obstructive pulmonary disease exacerbations (AECOPD) have a significant negative impact on the quality of life and accelerate progression of the disease. Functional respiratory imaging (FRI) has the potential to better characterize this disease. The purpose of this study was to identify FRI parameters specific to AECOPD and assess their ability to predict future AECOPD, by use of machine learning algorithms, enabling a better understanding and quantification of disease manifestation and progression. A multicenter cohort of 62 patients with COPD was analyzed. FRI obtained from baseline high resolution CT data (unenhanced and volume gated), clinical, and pulmonary function test were analyzed and incorporated into machine learning algorithms. A total of 11 baseline FRI parameters could significantly distinguish ( p < 0.05) the development of AECOPD from a stable period. In contrast, no baseline clinical or pulmonary function test parameters allowed significant classification. Furthermore, using Support Vector Machines, an accuracy of 80.65% and positive predictive value of 82.35% could be obtained by combining baseline FRI features such as total specific image-based airway volume and total specific image-based airway resistance, measured at functional residual capacity. Patients who developed an AECOPD, showed significantly smaller airway volumes and (hence) significantly higher airway resistances at baseline. This study indicates that FRI is a sensitive tool (PPV 82.35%) for predicting future AECOPD on a patient specific level in contrast to classical clinical parameters.

Effect of continuous-infusion antibiotic therapy on pulmonary function of patients with cystic fibrosis: A cross-sectional study

Background: Cystic fibrosis (CF) is associated with frequent pulmonary exacerbations which increase the mortality risk. Therefore, most CF patients are chronically colonized with respiratory pathogens, the most common being Pseudomonas aeruginosa. Multidrug-resistant organisms are a major problem in CF patients. It’s been hypothesized that continuous-infusion antipseudomonal beta-lactam therapy in CF maintains serum concentrations above the minimum inhibitory concentration of susceptible strains and is more likely than intermittent infusion to achieve optimal pharmacodynamic targets for some intermediate and resistant strains of P. aeruginosa. The most extensively studied antibiotic for continuous-infusion protocol in CF is ceftazidime, which has been shown to improve lung function (forced expiratory volume in 1 second and forced vital capacity) and to increase pulmonary exacerbation free time. There have been no studies to evaluate the cost effectiveness or impact on quality of life of continuous infusion versus intermittent infusion antibiotic therapy in patients with CF. Our study aims to investigate the effect of continuous-infusion antibiotic therapy on pulmonary function. Methods: Cross sectional study of CF patients who were admitted to our hospital with acute pulmonary exacerbations between 1/1/2010 and 12/31/2016 and received parenteral antibiotics. We investigated the effect of use of continuous versus intermittent infusion of intravenous antibiotics on the pulmonary function (FEV1% predicted). Results: Intermittent infusion protocol was found to have a very small advantage over continuous infusion protocol on pulmonary function; however this difference is not statistically significant (p=0.0049). The longer the duration of antibiotics, the slightly better the pulmonary function at the end of the treatment, but the difference was not significant (p=0.2543). Conclusions: Even though we could not draw meaningful conclusions from our data, we would like bring attention to this subject because it carries an important therapeutic value for CF patients.