Ceftolozane/tazobactam for Pseudomonas aeruginosa pulmonary exacerbations in cystic fibrosis adult patients: a case series

ABSTRACTPractitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

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Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02327-20 ◽

2020 ◽

pp. AAC.02327-20 ◽

Cited By ~ 1

Author(s):

Claire L Keating ◽

Jonathan B Zuckerman ◽

Pradeep K Singh ◽

Matthew McKevitt ◽

Oksana Gurtovaya ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Lung Function ◽

Clinical Outcomes ◽

Primary Endpoint ◽

The United States ◽

Study Endpoint ◽

Primary Study ◽

Antibiotic Exposure ◽

Pulmonary Exacerbations

Rationale: Approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect susceptibility profiles of Pseudomonas aeruginosa (PA) isolates from cystic fibrosis (CF) patients.Objective: This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic PA infection.Methods: Sputum cultures were collected annually (2011-2016). The primary study endpoint was the proportion of subjects whose least susceptible PA isolate had an aztreonam minimum inhibitory concentration (MIC) that was >8 μg/mL (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and FEV1% predicted were obtained from the CF Foundation Patient Registry and compared between subjects meeting/not meeting the primary endpoint.Results: 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13-22%) met the primary endpoint each year; and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual decline in lung function was comparable for subjects meeting/not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it.Conclusions: Aztreonam susceptibility of PA remained consistent during the 5-year study. The relationship between PA isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with accelerated decline in lung function, but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure.

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Use of Telavancin for the Treatment of Methicillin-Resistant Staphylococcus aureus-Associated Pulmonary Exacerbations in Patients With Cystic Fibrosis: A Retrospective Case Series

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw172.933 ◽

2016 ◽

Vol 3 (suppl_1) ◽

Cited By ~ 2

Author(s):

Katrina Mayr ◽

Louise-Marie Oleksiuk ◽

Keven Robinson ◽

Michael Myerburg ◽

Joseph Pilewski

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Case Series ◽

Retrospective Case ◽

Methicillin Resistant ◽

Retrospective Case Series ◽

Pulmonary Exacerbations

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Sera from Adult Patients with Cystic Fibrosis Contain Antibodies to Pseudomonas aeruginosa Type III Apparatus

Infection and Immunity ◽

10.1128/iai.69.2.1185-1188.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 1185-1188 ◽

Cited By ~ 32

Author(s):

Joel Moss ◽

Mary E. Ehrmantraut ◽

Bruce D. Banwart ◽

Dara W. Frank ◽

Joseph T. Barbieri

Keyword(s):

Cystic Fibrosis ◽

Immune Response ◽

Pseudomonas Aeruginosa ◽

Adult Patients ◽

Eukaryotic Cells ◽

Type Iii

ABSTRACT Expression of type III proteins of Pseudomonas aeruginosa in patients with cystic fibrosis (CF) was investigated by measuring the immune response against components of the type III pathway. Twenty-three of the 33 sera contained antibodies against PcrV, a protein involved in translocation of type III cytotoxins into eukaryotic cells, and 11 of 33 had antibodies against ExoS, while most CF sera contained antibodies against PopB and PopD, components of the type III apparatus. These data indicate that P. aeruginosacommonly expresses components of the type III translocation apparatus in adult CF patients.

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