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7. Individual meropenem epithelial lining fluid and plasma PK/PD target attainment

Author

Rohani, Roxane, primary, Yarnold, Paul R., additional, Scheetz, Marc H., additional, Neely, Michael N., additional, Kang, Mengjia, additional, Donnelly, Helen K., additional, Dedicatoria, Kay, additional, Nozick, Sophie H., additional, Medernach, Rachel L., additional, Hauser, Alan R., additional, Ozer, Egon A., additional, Diaz, Estefani, additional, Misharin, Alexander V., additional, Wunderink, Richard G., additional, and Rhodes, Nathaniel J., additional

Published
2023
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10. 2560. Individual Meropenem Epithelial Lining Fluid and Plasma PK/PD Target Attainment in Patients with Pneumonia

Author

Rohani, Roxane, primary, Yarnold, Paul R, additional, Scheetz, Marc H, additional, Neely, Michael N, additional, Kang, Mengjia, additional, Donnelly, Helen K, additional, Dedicatoria, Kay, additional, Nozick, Sophia, additional, Medernach, Rachel, additional, Hauser, Alan R, additional, Ozer, Egon A, additional, Diaz, Estefani, additional, Misharin, Alexander V, additional, Wunderink, Richard G, additional, and Rhodes, Nathaniel J, additional

Published
2023
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11. 1275. Impact of a bundled antimicrobial stewardship intervention leveraging frontline pharmacist response to rapid blood culture diagnostics at an academic medical center and community hospital

Author

Bajer, Kevin, primary, Bertram, Christie M, additional, Weslander, Erin, additional, Qi, Chao, additional, Moore, William J, additional, Polisetty, Radhika S, additional, Postelnick, Mike, additional, Zembower, Teresa, additional, Wronkiewicz, Stephanie, additional, Rhodes, Nathaniel J, additional, Kling, Kendall, additional, and Sutton, Sarah, additional

Published
2023
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16. Individual target pharmacokinetic/pharmacodynamic attainment rates among meropenem-treated patients admitted to the ICU with hospital-acquired pneumonia

Author

Rohani, Roxane, Scheetz, Marc H, Donnelly, Helen K, Donayre, Alvaro, Kang, Mengjia, Diaz, Estefani, Dedicatoria, Kay, Hauser, Alan R, Ozer, Egon A, Nozick, Sophia, Qi, Chao, Pawlowski, Anna E, Neely, Michael N, Misharin, Alexander V, Wunderink, Richard G, and Rhodes, Nathaniel J

Subjects
Pharmacology, Microbiology (medical), Critical Illness, Meropenem, Microbial Sensitivity Tests, Pneumonia, Hospitals, Anti-Bacterial Agents, Intensive Care Units, Infectious Diseases, Humans, Pharmacology (medical), Prospective Studies, Original Research
Abstract

Objectives Critical illness reduces β-lactam pharmacokinetic/pharmacodynamic (PK/PD) attainment. We sought to quantify PK/PD attainment in patients with hospital-acquired pneumonia. Methods Meropenem plasma PK data (n = 70 patients) were modelled, PK/PD attainment rates were calculated for empirical and definitive targets, and between-patient variability was quantified [as a coefficient of variation (CV%)]. Results Attainment of 100% T>4×MIC was variable for both empirical (CV% = 92) and directed (CV% = 33%) treatment. Conclusions Individualization is required to achieve suggested PK/PD targets in critically ill patients.

Published
2022

22. Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults.

Author

Chang, Jack, Liu, Jiajun, Alshaer, Mohammad H, Venugopalan, Veena, Maranchick, Nicole, Peloquin, Charles A, Rhodes, Nathaniel J, and Scheetz, Marc H

Subjects
CRITICALLY ill, CEFEPIME, DRUG monitoring, SIMULATED patients, PARAMETERS (Statistics)
Abstract

Objective To investigate and describe the variability in cefepime exposures among 'real-world', critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations. Methods A cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2). Variability in the relationship between cefepime clearance and creatinine clearance (CrCL) was visualized, and a random, representative sample of 10 simulated patients was utilized to illustrate variability in cefepime exposures. Results A total of 75 adult medical ICU patients (52% female) and 98 serum cefepime samples were included in the study. Population parameter estimates for cefepime displayed a wide range of variation in Model 1 (CV: 45% to 95%), with low bias at the individual level at 0.226 mg/L but high bias in the population model 10.6 mg/L. Model 2 displayed similar fits, demonstrating that correcting for individual patient creatinine clearance slightly improves the bias of the population model (bias = 4.31 mg/L). Among 10 simulated patients that a clinician would deem similar from a dosing perspective (i.e. equivalent creatinine clearance), maximum concentrations after three simulated doses varied more than 8-fold from 41.2 to 339 mg/L at the 5th and 95th percentiles, and clearance profiles were highly different. Conclusion Creatinine clearance estimates alone are inadequate for predicting cefepime exposures. Wide variations in cefepime exposure exist among ICU patients, even for those with similar kidney function estimates. Current population adjustment schemes based solely on creatinine clearance will result in unintended high and low exposures leading to safety and efficacy concerns, respectively. [ABSTRACT FROM AUTHOR]

Published
2023
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33. Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury

Author

Locci, Emanuela, primary, Liu, Jiajun, additional, Pais, Gwendolyn M., additional, Chighine, Alberto, additional, Kahnamoei, Dariusc Andrea, additional, Xanthos, Theodoros, additional, Chalkias, Athanasios, additional, Lee, Andrew, additional, Hauser, Alan R., additional, Chang, Jack, additional, Rhodes, Nathaniel J., additional, d'Aloja, Ernesto, additional, and Scheetz, Marc H., additional

Published
2022
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35. Antibiotic choice for Group B Streptococcus prophylaxis in mothers with reported penicillin allergy and associated newborn outcomes.

Author

Snider, Josephine B., Mithal, Leena B., Kwah, Jason H., Rhodes, Nathaniel J., and Son, Moeun

Subjects
STREPTOCOCCUS agalactiae, SKIN tests, ANTIBIOTIC prophylaxis, NEONATAL intensive care units, PENICILLIN, BETA lactam antibiotics, ANTIBIOTICS
Abstract

Objective: To evaluate the choice of antibiotic used for intrapartum Group B Streptococcus (GBS) prophylaxis in pregnant individuals with reported penicillin allergies compared to those without reported penicillin allergies and investigate whether there are associated differences in neonatal outcomes. Study Design: This retrospective cohort study included mother-infant dyads of GBS positive pregnant individuals who labored and delivered newborns ≥ 35 weeks of gestation at a high-volume urban hospital (2005–2018). The type of antibiotic administered to the mothers for GBS prophylaxis (beta-lactam prophylaxis defined as penicillin-class drug or cefazolin; alternative prophylaxis defined as vancomycin or clindamycin) was compared between those with a penicillin allergy documented in their medical record versus those who did not. Neonatal outcomes included number of postnatal blood draws, antibiotic administration, neonatal intensive care unit (NICU) admission, bacteremia, and hospital length of stay and were compared between groups. Bivariable and multivariable analyses were performed. Results: Of 11,334 mother-infant pairs, 1170 (10.3%) mothers had a penicillin allergy documented in their medical record. Of them, 49 (4.2%) received a penicillin, 259 (22.1%) received cefazolin, 449 (38.4%) received clindamycin, and 413 (35.3%) received vancomycin. Patients with a reported penicillin allergy were significantly more likely to receive alternative GBS prophylaxis compared to those without penicillin allergy (73.7% vs. 0.2%, p < 0.01). Neonates of patients who received alternative GBS prophylaxis were significantly more likely to undergo a postnatal lab draw compared to neonates of patients who received beta-lactam antibiotics (20.8% vs. 17.3%, OR 1.25 (95% CI 1.08–1.46)). This significant association persisted after adjusting for potential confounders (aOR 1.23, 95% CI 1.06–1.43). There were no other significant differences seen in other newborn outcomes. Conclusion: Pregnant individuals who report a penicillin allergy were more likely to receive alternative antibiotics for GBS prophylaxis compared to those without a penicillin allergy. This was associated with an increased frequency of postnatal blood draws among neonates of mothers with a reported penicillin allergy. Brief summary: Administration of alternative intrapartum antibiotic prophylaxis with vancomycin or clindamycin is common in individuals with self-reported penicillin allergy, and maternal alternative antibiotic administration may impact neonatal care, particularly via increased lab draws. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Impact of early antimicrobial stewardship intervention in patients with positive blood cultures: results from a randomized comparative study

Author

O'Donnell, J Nicholas, primary, Rhodes, Nathaniel J, additional, Miglis, Cristina M, additional, Zembower, Teresa R., additional, Qi, Chao, additional, Hoff, Brian M, additional, Barr, Viktorija O, additional, Gilbert, Elise M., additional, Bolon, Maureen K, additional, Malczynski, Michael, additional, Gener, Joshua, additional, Tran, Chau, additional, Catovic, Lejla, additional, Postelnick, Michael J., additional, Sutton, Sarah H, additional, and Scheetz, Marc H, additional

Published
2021
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42. Of Rats and Men: a Translational Model To Understand Vancomycin Pharmacokinetic/Toxicodynamic Relationships

Author

Scheetz, Marc H., primary, Pais, Gwendolyn M., additional, Lodise, Thomas P., additional, Tong, Steven Y. C., additional, Davis, Joshua S., additional, O’Donnell, J. Nicholas, additional, Liu, Jiajun, additional, Neely, Michael, additional, Prozialeck, Walter C., additional, Lamar, Peter C., additional, Rhodes, Nathaniel J., additional, Holland, Thomas, additional, and Avedissian, Sean N., additional

Published
2021
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46. Characterizing Risk Factors for Clostridioides difficile Infection among Hospitalized Patients with Community-Acquired Pneumonia

Author

Rhodes, Nathaniel J., primary, Jozefczyk, Caroline C., additional, Moore, W. Justin, additional, Yarnold, Paul R., additional, Harkabuz, Karolina, additional, Maxwell, Robert, additional, Sutton, Sarah H., additional, Silkaitis, Christina, additional, Qi, Chao, additional, Wunderink, Richard G., additional, and Zembower, Teresa R., additional

Published
2021
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49. Urinary Metabolomics from a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury

Author

Locci, Emanuela, primary, Liu, Jiajun, additional, Pais, Gwendolyn M., additional, Chighine, Alberto, additional, Kahnamoei, Dariusc Andrea, additional, Xanthos, Theodoros, additional, Chalkias, Athanasios, additional, Lee, Andrew, additional, Hauser, Alan R., additional, Chang, Jack, additional, Rhodes, Nathaniel J., additional, d’Aloja, Ernesto, additional, and Scheetz, Marc H., additional

Published
2021
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