Association of Intensity of Antipseudomonal Antibiotic Therapy With Risk of Treatment-Emergent Organisms in Children With Cystic Fibrosis and Newly Acquired Pseudomonas Aeruginosa

2021 ◽  
Author(s):  
Jonathan D Cogen ◽  
Frankline M Onchiri ◽  
Nicole Mayer Hamblett ◽  
Ronald L Gibson ◽  
Wayne J Morgan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Proportional Hazards ◽  
Controlled Trial ◽  
Multidrug Resistant ◽  
Cox Proportional Hazards ◽  
Achromobacter Xylosoxidans ◽  
Drug Resistant ◽  
Antibiotic Exposure ◽  
Cox Proportional Hazards Models

Abstract Background While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection. Methods We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics or ever versus never treatment with intravenous antipseudomonal antibiotics during the 18 months of EPIC CT participation. Primary outcomes were risks of acquisition of several respiratory organisms during 5 years of follow-up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism. Results Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR, 1.24; 95% CI: 1.02–1.50; P = .03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR, 2.47; 95% CI: 1.28–4.78; P = .01) and MRSA (HR, 1.57; 95% CI: 1.03–2.40; P = .04). Conclusions Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing risk of acquisition of drug-resistant organisms.

Hypoxemia following generalized convulsive seizures

Neurology ◽  
2018 ◽  
Vol 92 (3) ◽  
pp. e183-e193 ◽  
Author(s):  
Sylvain Rheims ◽  
Blanca Mercedes Alvarez ◽  
Veriano Alexandre ◽  
Jonathan Curot ◽  
Louis Maillard ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Focal Epilepsy ◽  
Cox Proportional Hazards ◽  
Drug Resistant ◽  
Early Recovery ◽  
Early Administration ◽  
Cox Proportional Hazards Models ◽  
Eeg Recordings ◽  
Convulsive Seizures ◽  
Video Eeg

ObjectiveTo analyze the factors that determine the occurrence or severity of postictal hypoxemia in the immediate aftermath of a generalized convulsive seizure (GCS).MethodsWe reviewed the video-EEG recordings of 1,006 patients with drug-resistant focal epilepsy included in the REPO2MSE study to identify those with ≥1 GCS and pulse oximetry (SpO2) measurement. Factors determining recovery of SpO2 ≥ 90% were investigated using Cox proportional hazards models. Association between SpO2 nadir and person- or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures.ResultsA total of 107 GCS in 73 patients were analyzed. A transient hypoxemia was observed in 92 GCS (86%). Rate of GCS with SpO2 <70% dropped from 40% to 21% when oxygen was administered early (p = 0.046). Early recovery of SpO2 ≥90% was associated with early administration of oxygen (p = 0.004), absence of postictal generalized EEG suppression (PGES) (p = 0.014), and extratemporal lobe epilepsy (p = 0.001). Lack of early administration of O2 (p = 0.003), occurrence of PGES (p = 0.018), and occurrence of ictal hypoxemia during the focal phase (p = 0.022) were associated with lower SpO2 nadir.ConclusionPostictal hypoxemia was observed in the immediate aftermath of nearly all GCS but administration of oxygen had a strong preventive effect. Severity of postictal hypoxemia was greater in temporal lobe epilepsy and when hypoxemia was already observed before the onset of secondary GCS.

scholarly journals Infectious Diseases Consultation Reduces 30-Day and 1-Year All-Cause Mortality for Multidrug-Resistant Organism Infections

2018 ◽  
Vol 5 (3) ◽  
Author(s):  
Jason P Burnham ◽  
Margaret A Olsen ◽  
Dustin Stwalley ◽  
Jennie H Kwon ◽  
Hilary M Babcock ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Proportional Hazards ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Resistant Organism ◽  
Tertiary Referral Center ◽  
Cox Proportional Hazards Models ◽  
Polymicrobial Infections

Abstract Background Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections. Methods This study was conducted with a retrospective cohort (January 1, 2006–October 1, 2015) at an academic tertiary referral center. We identified patients with MDROs in a sterile site or bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within 1 year of index culture were identified, and the association of ID consultation with these outcomes was determined using Cox proportional hazards models with inverse weighting by the propensity score for ID consultation. Results A total of 4214 patients with MDRO infections were identified. ID consultation was significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.63; and HR, 0.73, 95% CI, 0.61–0.86) and Enterobacteriaceae (HR, 0.41; 95% CI, 0.27–0.64; and HR, 0.74; 95% CI, 0.59–0.94), and 30-day mortality for polymicrobial infections (HR, 0.51; 95% CI, 0.31–0.86) but not Acinetobacter or Pseudomonas. For resistant Enterococcus, ID consultation was marginally associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62–1.06). ID consultation was associated with reduced 30-day readmission for resistant Enterobacteriaceae. Conclusions ID consultation was associated with significant reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was no association between ID consultation and mortality for patients with resistant Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes. Our results suggest that ID consultation may be beneficial for patients with some MDRO infections.

scholarly journals 1594. Ceftolozane–Tazobactam Demonstrates Higher In Vitro Susceptibility than Ceftazidime–Avibactam Against Pseudomonas aeruginosa Isolated from Respiratory Tract of Adult Cystic Fibrosis Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S581-S582
Author(s):  
Patrick James Nolan ◽  
Tiffeny Smith ◽  
James D Finklea ◽  
Leah Cohen ◽  
Raksha Jain
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
In Vitro Susceptibility

Abstract Background Pseudomonas aeruginosa is a commonly isolated pathogen in adults with cystic fibrosis (CF). Antimicrobial resistance is an escalating problem due to chronic colonization and frequent antimicrobial exposure. Ceftolozane–tazobactam (C/T) and ceftazidime–avibactam (CZA) exhibit promising activity against antimicrobial-resistant organisms, including P. aeruginosa. In this study, we compared in vitro activity of C/T and CZA against P. aeruginosa isolated from respiratory cultures obtained from adult patients with CF. Methods This is a retrospective study of respiratory cultures positive for P. aeruginosa collected from adult CF patients between January 1, 2015 to November 30, 2018. The first isolate per patient per year that underwent susceptibility testing for C/T, CZA, and colistin were included in the study. All isolates underwent in-house susceptibility testing for 9 anti-pseudomonal agents according to the methodology established by the Clinical Laboratory Standards Institute (CLSI). Susceptibility testing of C/T, CZA, and colistin were performed by a reference lab. Isolates were classified into 3 drug-resistant categories using the following definition: multidrug-resistant (MDR) non-susceptible (NS) to ≥1 agent in ≥3 different antimicrobial classes, extensive drug-resistant (XDR) NS to 4 or 5 different classes, and pan drug-resistant (PDR) NS to all 6 classes except colistin. Results Forty-two P. aeruginosa respiratory isolates from 32 patients with CF were included. The overall susceptibility to C/T and CZA was 59.5% and 42.9%, respectively. Thirty-eight (90%) isolates were considered MDR with susceptibility of 55.3% to C/T and 44.7% to CZA. Among the 11 XDR isolates, susceptibility to C/T was 81.8% vs. CZA 72.7%. Susceptibility to C/T vs. CZA was also higher (37.5% vs. 25%) among the 24 PDR isolates. Conclusion Among P. aeruginosa isolated from CF respiratory cultures, C/T appears to have better in vitro activity compared with CZA, and remained true among isolates considered XDR and PDR. These results suggest using C/T while awaiting susceptibilities when standard anti-pseudomonal agents cannot be used. Future studies evaluating clinical outcomes for the treatment of pulmonary CF exacerbations are needed to assess the applicability of in vitro susceptibility data. Disclosures All authors: No reported disclosures.

scholarly journals Impact of Pseudomonas aeruginosa Isolation on Mortality and Outcomes in an Outpatient Chronic Obstructive Pulmonary Disease Cohort

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
David M Jacobs ◽  
Heather M Ochs-Balcom ◽  
Katia Noyes ◽  
Jiwei Zhao ◽  
Wai Yin Leung ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pseudomonas Aeruginosa ◽  
Pulmonary Disease ◽  
Proportional Hazards ◽  
Outpatient Setting ◽  
Cox Proportional Hazards ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Hospitalization Rates ◽  
Cox Proportional Hazards Models

Abstract Background Tracheobronchial colonization by Pseudomonas aeruginosa (PA) has been shown to negatively impact outcomes in cystic fibrosis and bronchiectasis. There is uncertainty whether the same association is prevalent in chronic obstructive pulmonary disease (COPD), especially in the outpatient setting. Our objective was to determine (1) whether PA isolation is associated with mortality and (2) changes in exacerbation and hospitalization rates within a longitudinal cohort of COPD outpatients. Methods Pseudomonas aeruginosa colonization was ascertained in monthly sputum cultures in a prospective cohort of COPD patients from 1994 to 2014. All-cause mortality was compared between patients who were colonized during their follow-up period (PA+) and those who remained free of colonization (PA−); Cox proportional hazards models were used. Exacerbation and hospitalization rates were evaluated by 2-rate χ 2 and segmented regression analysis for 12 months before and 24 months after PA isolation. Results Pseudomonas aeruginosa was isolated from sputum in 73 of 181 (40%) patients. Increased mortality was seen with PA isolation: 56 of 73 (77%) PA+ patients died compared with 73 of 108 (68%) PA− patients (P = .004). In adjusted models, PA+ patients had a 47% higher risk of mortality (adjusted hazard ratio = 1.47; 95% confidence interval, 1.03–2.11; P = .04). Exacerbation rates were higher for the PA+ group during preisolation (15.4 vs 9.0 per 100 person-months, P &lt; .001) and postisolation periods (15.7 vs 7.5, P &lt; .001). Hospitalization rates were higher during the postisolation period among PA+ patients (6.25 vs 2.44, P &lt; .001). Conclusions Tracheobronchial colonization by PA in COPD outpatients was associated with higher morbidity and mortality. This suggests that PA likely contributes to adverse clinical outcomes rather than just a marker of worsening disease.

scholarly journals A contemporary survival analysis of individuals with cystic fibrosis: a cohort study

2014 ◽  
Vol 45 (3) ◽  
pp. 670-679 ◽  
Author(s):  
Anne L. Stephenson ◽  
Melissa Tom ◽  
Yves Berthiaume ◽  
Lianne G. Singer ◽  
Shawn D. Aaron ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Proportional Hazards ◽  
Patient Characteristics ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Cox Proportional Hazards Models ◽  
Increased Risk

Previously established predictors of survival may no longer apply in the current era of cystic fibrosis (CF) care. Our objective was to identify risk factors associated with survival in a contemporary CF population.We used the Canadian CF Registry, a population-based cohort, to calculate median age of survival and summarise patient characteristics from 1990 to 2012. Clinical, demographic and geographical factors, and survival were estimated for a contemporary cohort (2000–2012) using Cox proportional hazards models.There were 5787 individuals in the registry between 1990 and 2012. Median survival age increased from 31.9 years (95% CI 28.3–35.2 years) in 1990 to 49.7 years (95% CI 46.1–52.2 years) in the most current 5-year window ending in 2012. Median forced expiratory volume in 1 s improved (p=0.04) and fewer subjects were malnourished (p<0.001) over time. Malnourished patients (hazard ratio (HR) 2.1, 95% CI 1.6–2.8), those with multiple exacerbations (HR 4.5, 95% CI 3.2–6.4) and women with CF-related diabetes (HR 1.8, 95% CI 1.2–2.7) were at increased risk of death.Life expectancy in Canadians with CF is increasing. Modifiable risk factors such as malnutrition and pulmonary exacerbations are associated with an increased risk of death. The sex gap in CF survival may be explained by an increased hazard for death in women with CF-related diabetes.

scholarly journals Biomarkers of Systemic Inflammation and Growth in Early Infancy are Associated with Stunting in Young Tanzanian Children

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1158 ◽  
Author(s):  
Sana Syed ◽  
Karim Manji ◽  
Christine McDonald ◽  
Rodrick Kisenge ◽  
Said Aboud ◽  
...  
Keyword(s):  
Growth Factor ◽  
Systemic Inflammation ◽  
Proportional Hazards ◽  
Controlled Trial ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
Insulin Like Growth Factor ◽  
Reactive Protein ◽  
Cox Proportional Hazards Models ◽  
Z Scores

Stunting can afflict up to one-third of children in resource-constrained countries. We hypothesized that low-grade systemic inflammation (defined as elevations in serum C-reactive protein or alpha-1-acid glycoprotein) in infancy suppresses the growth hormone–insulin-like growth factor (IGF) axis and is associated with subsequent stunting. Blood samples of 590 children from periurban Dar es Salaam, Tanzania, were obtained at 6 weeks and 6 months of age as part of a randomized controlled trial. Primary outcomes were stunting, underweight, and wasting (defined as length-for-age, weight-for-age and weight-for-length z-scores < −2) between randomization and endline (18 months after randomization). Cox proportional hazards models were constructed to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of time to first stunting, underweight, and wasting as outcomes, with measures of systemic inflammation, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) as exposures, adjusting for numerous demographic and clinical variables. The incidences of subsequent stunting, underweight, and wasting were 26%, 20%, and 18%, respectively. In multivariate analyses, systemic inflammation at 6 weeks of age was significantly associated with stunting (HR: 2.14, 95% CI: 1.23, 3.72; p = 0.002). Children with higher levels of IGF-1 at 6 weeks were less likely to become stunted (HR: 0.58, 95% CI: 0.37, 0.93; p for trend = 0.019); a similar trend was noted in children with higher levels of IGF-1 at 6 months of age (HR: 0.50, 95% CI: 0.22, 1.12; p for trend = 0.07). Systemic inflammation occurs as early as 6 weeks of age and is associated with the risk of future stunting among Tanzanian children.

scholarly journals 1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S795
Author(s):  
Mary Francine P Chua ◽  
Syeda Sara Nida ◽  
Jerry Lawhorn ◽  
Janak Koirala
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Additive Effect ◽  
Teaching Hospitals ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Synergy Testing ◽  
Concentration Indices

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, &gt;0.5 to &lt;1, &gt;1 to &lt;4, and &gt;4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 &gt;32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

scholarly journals In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis

2021 ◽  
Vol 9 (3) ◽  
pp. 478
Author(s):  
Ersilia Vita Fiscarelli ◽  
Martina Rossitto ◽  
Paola Rosati ◽  
Nour Essa ◽  
Valentina Crocetta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
In Vitro Test ◽  
Chronic Infections ◽  
Hospital Environments ◽  
Vitro Test ◽  
General Reliability ◽  
Phage Activity

As disease worsens in patients with cystic fibrosis (CF), Pseudomonas aeruginosa (PA) colonizes the lungs, causing pulmonary failure and mortality. Progressively, PA forms typical biofilms, and antibiotic treatments determine multidrug-resistant (MDR) PA strains. To advance new therapies against MDR PA, research has reappraised bacteriophages (phages), viruses naturally infecting bacteria. Because few in vitro studies have tested phages on CF PA biofilms, general reliability remains unclear. This study aimed to test in vitro newly isolated environmental phage activity against PA isolates from patients with CF at Bambino Gesù Children’s Hospital (OBG), Rome, Italy. After testing in vitro phage activities, we combined phages with amikacin, meropenem, and tobramycin against CF PA pre-formed biofilms. We also investigated new emerging morphotypes and bacterial regrowth. We obtained 22 newly isolated phages from various environments, including OBG. In about 94% of 32 CF PA isolates tested, these phages showed in vitro PA lysis. Despite poor efficacy against chronic CF PA, five selected-lytic-phages (Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG) showed wide host activity. The Φ4_ZP1-meropenem and Φ14_OBG-tobramycin combinations significantly reduced CF PA biofilms (p < 0.001). To advance potential combined phage-antibiotic therapy, we envisage further in vitro test combinations with newly isolated phages, including those from hospital environments, against CF PA biofilms from early and chronic infections.

Sign in / Sign up

Export Citation Format

Share Document