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4. The authors reply

Author

Lawandi, Alexander, Oshiro, Marissa, Warner, Sarah, Diao, Guoqing, Strich, Jeffrey R., Babiker, Ahmed, Rhee, Chanu, Klompas, Michael, Danner, Robert L., and Kadri, Sameer S.

Published
2024
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7. Epidemiology and Outcomes of Antibiotic De-escalation in Patients With Suspected Sepsis in US Hospitals.

Author

Kam, Kai Qian, Chen, Tom, Kadri, Sameer S, Lawandi, Alexander, Yek, Christina, Walker, Morgan, Warner, Sarah, Fram, David, Chen, Huai-Chun, Shappell, Claire N, DelloStritto, Laura, Jin, Robert, Klompas, Michael, and Rhee, Chanu

Abstract

Background Little is known about the frequency, hospital-level variation, predictors, and outcomes of antibiotic de-escalation in suspected sepsis. Methods We retrospectively analyzed adults admitted to 236 US hospitals from 2017–2021 with suspected sepsis (defined by blood culture draw, lactate measurement, and intravenous antibiotic administration) who were initially treated with ≥2 days of anti–methicillin-resistant Staphylococcus aureus (MRSA) and anti-pseudomonal antibiotics but had no resistant organisms that required these agents identified through hospital day 4. De-escalation was defined as stopping anti-MRSA and anti-pseudomonal antibiotics or switching to narrower antibiotics by day 4. We created a propensity score for de-escalation using 82 hospital and clinical variables; matched de-escalated to non–de-escalated patients; and assessed associations between de-escalation and outcomes. Results Among 124 577 patients, antibiotics were de-escalated in 36 806 (29.5%): narrowing in 27 177 (21.8%), cessation in 9629 (7.7%). De-escalation rates varied between hospitals (median, 29.4%; interquartile range, 21.3%–38.0%). Predictors of de-escalation included less severe disease on day 3–4, positive cultures for nonresistant organisms, and negative/absent MRSA nasal swabs. De-escalation was more common in medium, large, and teaching hospitals in the Northeast and Midwest. De-escalation was associated with lower adjusted risks for acute kidney injury (AKI) (odds ratio [OR], 0.80; 95% confidence interval [CI],.76–.84), intensive-care unit (ICU) admission after day 4 (OR, 0.59; 95% CI,.52–.66), and in-hospital mortality (OR, 0.92; 95% CI,.86–.996). Conclusions Antibiotic de-escalation in suspected sepsis is infrequent, variable across hospitals, linked with clinical and microbiologic factors, and associated with lower risk for AKI, ICU admission, and in-hospital mortality. [ABSTRACT FROM AUTHOR]

Published
2025
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9. Impaired apoptosis underlying lymphoproliferative disease in a patient with haploinsufficient NFKB1 deficiency.

Author

Roussel, Lucie, Bernier, Stephane, Perez, Anna, Sun, Yichun, Angers, Isabelle, Laneuville, Pierre, Lawandi, Alexander, and Vinh, Donald C.

Subjects
POSITRON emission tomography computed tomography, HEMATOPOIETIC stem cell transplantation, CELL receptors, MONONUCLEAR leukocytes, LYMPHOBLASTOID cell lines, NECROSIS, TALL-1 (Protein)
Abstract

The article discusses a case study of a 41-year-old male with NFkB1 haploinsufficiency, a condition associated with lymphoproliferative disease (LPD). The patient exhibited chronic lymphadenopathy and impaired apoptosis, leading to resistance to cell death triggers. The study highlights the importance of understanding the mechanisms underlying LPD in NFkB1 haploinsufficient patients and suggests potential therapeutic targets for further research. The findings emphasize the need for personalized monitoring and treatment strategies for individuals with this condition. [Extracted from the article]

Published
2024
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14. 1110. Why has Utilization of Novel Gram-negative Antibiotics been Sluggish in U.S. Hospitals? A Retrospective Cohort Study to Inform Future Antibiotic Development and Market Entry Rewards

Author

Strich, Jeffrey R, primary, Ullah Mishuk, Ahmed, additional, Lawandi, Alexander, additional, Diao, Guoqing, additional, Warner, Sarah, additional, Li, Willy, additional, Demirkale, Cumhur Y, additional, Mancera, Alex, additional, Walker, Morgan, additional, Yek, Christina, additional, Neupane, Maniraj, additional, De Jonge, Nathaniel, additional, and Kadri, Sameer S, additional

Published
2023
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15. Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals: A Retrospective Cohort Study.

Author

Strich, Jeffrey R., Mishuk, Ahmed, Diao, Guoqing, Lawandi, Alexander, Li, Willy, Demirkale, Cumhur Y., Babiker, Ahmed, Mancera, Alex, Swihart, Bruce J., Walker, Morgan, Yek, Christina, Neupane, Maniraj, De Jonge, Nathaniel, Warner, Sarah, and Kadri, Sameer S.

Subjects
GRAM-negative bacteria, MEDICAL personnel, ANTIBIOTICS, COHORT analysis, MICROBIAL sensitivity tests, BURN patients
Abstract

Drug-resistant bacteria remain an ever-present danger to patients and patient safety. Understanding whether and how clinicians use recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development. This study sought to determine use patterns of recently approved gram-negative antibiotics and identify factors associated with their preferential use in patients with gram-negative infections. The study found that despite approval of 7 next-generation gram-negative antibiotics, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety–efficacy profiles. Visual Abstract. Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals: Drug-resistant bacteria remain an ever-present danger to patients and patient safety. Understanding whether and how clinicians use recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development. This study sought to determine use patterns of recently approved gram-negative antibiotics and identify factors associated with their preferential use in patients with gram-negative infections. The study found that despite approval of 7 next-generation gram-negative antibiotics, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety–efficacy profiles. Background: The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. Objective: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, plazomicin, eravacycline, imipenem–relebactam–cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics). Design: Retrospective cohort. Setting: 619 U.S. hospitals. Participants: Adult inpatients. Measurements: Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections. Results: Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane–tazobactam (approved 2014) and ceftazidime–avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including "reserve" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage. Limitation: Residual confounding. Conclusion: Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety–efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. Primary Funding Source: U.S. Food and Drug Administration; NIH Intramural Research Program. [ABSTRACT FROM AUTHOR]

Published
2024
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16. qSOFA does not predict bacteremia in patients with severe manifestations of sepsis

Author

Cheng, Matthew P, Paquette, Katryn, Lawandi, Alexander, Stabler, Sarah N, Akhter, Murtaza, Davidson, Adam C, Gavric, Marko, Jinah, Rehman, Saeed, Zahid, Demir, Koray, Sangsari, Sassan, Huang, Kelly, Mahpour, Amirali, Shamatutu, Chris, Caya, Chelsea, Troquet, Jean-Marc, Clark, Greg, Rush, Barret, Wong, Titus, Stenstrom, Robert, Sweet, David, and Yansouni, Cedric P

Subjects
Microbiology (medical), Infectious Diseases, Brief Report
Abstract

BACKGROUND: Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. METHODS: We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. RESULTS: Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. CONCLUSIONS: Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

Published
2022
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18. Association between minimum inhibitory concentration values and mortality risk in patients with Stenotrophomonas maltophilia infections: a retrospective cohort study of electronic health records from 148 US hospitals

Author

Sarzynski, Sadia H, primary, Lawandi, Alexander, additional, Warner, Sarah, additional, Demirkale, Cumhur Y, additional, Strich, Jeffrey R, additional, Dekker, John P, additional, Babiker, Ahmed, additional, Li, Willy, additional, and Kadri, Sameer S, additional

Published
2023
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20. 1649. Ceftolozane-Tazobactam or Ceftazidime-Avibactam Versus Best Available Therapy in the Treatment of Difficult-to-Treat Pseudomonas aeruginosa Infections: a Retrospective Comparative Effectiveness Analysis of 195 U.S. Hospitals, 2016–2020

Author

Lawandi, Alexander, primary, Mishuk, Ahmed Ullah, additional, Yek, Christina, additional, Yu, Amy, additional, Li, Xiaobai, additional, Strich, Jeffrey R, additional, Sarzynski, Sadia, additional, Warner, Sarah, additional, and Kadri, Sameer S, additional

Published
2022
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21. 652. Ceftazidime-avibactam Alone or as Combination Therapy? Multicenter Retrospective Cohort Analysis of Clinical Outcomes in Patients with Carbapenem-resistant Gram-negative Infection

Author

Mishuk, Ahmed Ullah, primary, Strich, Jeffrey R, additional, Warner, Sarah, additional, Sun, Junfeng, additional, Malik, Seidu, additional, Lawandi, Alexander, additional, Kondo, Maiko, additional, Satlin, Michael J, additional, Chandorkar, Aditya, additional, Heil, Emily L, additional, Morales, Megan K, additional, Mathur, Anisha, additional, Timpone, Joseph, additional, Wooten, Darcy, additional, Sweeney, Daniel, additional, Pan, Jonathan, additional, Raybould, Jillian, additional, Bonne, Stephanie, additional, Colindres, Roberto, additional, Boucher, Helen W, additional, Buckman, Sara, additional, Furukawa, Daisuke, additional, Uslan, Daniel, additional, Hohmann, Samuel F, additional, and Kadri, Sameer S, additional

Published
2022
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24. Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial

Author

Sohani, Zahra N., primary, Butler-Laporte, Guillaume, additional, Aw, Andrew, additional, Belga, Sara, additional, Benedetti, Andrea, additional, Carignan, Alex, additional, Cheng, Matthew P., additional, Coburn, Bryan, additional, Costiniuk, Cecilia T, additional, Ezer, Nicole, additional, Gregson, Dan, additional, Johnson, Andrew, additional, Khwaja, Kosar, additional, Lawandi, Alexander, additional, Leung, Victor, additional, Lother, Sylvain, additional, MacFadden, Derek, additional, McGuinty, Michaeline, additional, Parkes, Leighanne, additional, Qureshi, Salman, additional, Roy, Valerie, additional, Rush, Barret, additional, Schwartz, Ilan, additional, So, Miranda, additional, Somayaji, Ranjani, additional, Tan, Darrell, additional, Trinh, Emilie, additional, Lee, Todd C., additional, and McDonald, Emily G., additional

Published
2022
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28. Suspected SARS-CoV-2 Reinfections: Incidence, Predictors, and Healthcare Use among Patients at 238 U.S. Healthcare Facilities, June 1, 2020- February 28, 2021

Author

Lawandi, Alexander, Warner, Sarah, Sun, Junfeng, Demirkale, Cumhur Y, Danner, Robert L, Klompas, Michael, Gundlapalli, Adi, Datta, Deblina, Harris, Aaron M, Morris, Sapna Bamrah, Natarajan, Pavithra, and Kadri, Sameer S

Subjects
AcademicSubjects/MED00290, SARS-CoV-2, Brief Report, Incidence, Reinfection, COVID-19, Humans, Female, Delivery of Health Care, Retrospective Studies
Abstract

In a retrospective cohort study, among 131 773 patients with previous coronavirus disease 2019 (COVID-19), reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was suspected in 253 patients (0.2%) at 238 US healthcare facilities between 1 June 2020 and 28 February 2021. Women displayed a higher cumulative reinfection risk. Healthcare burden and illness severity were similar between index and reinfection encounters.

Published
2021

30. The Reply

Author

Lee, Todd C., primary, Wilson, Marnie Goodwin, additional, Lawandi, Alexander, additional, and McDonald, Emily G., additional

Published
2021
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31. Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020

Author

Kadri, Sameer S., primary, Sun, Junfeng, additional, Lawandi, Alexander, additional, Strich, Jeffrey R., additional, Busch, Lindsay M., additional, Keller, Michael, additional, Babiker, Ahmed, additional, Yek, Christina, additional, Malik, Seidu, additional, Krack, Janell, additional, Dekker, John P., additional, Spaulding, Alicen B., additional, Ricotta, Emily, additional, Powers, John H., additional, Rhee, Chanu, additional, Klompas, Michael, additional, Athale, Janhavi, additional, Boehmer, Tegan K., additional, Gundlapalli, Adi V., additional, Bentley, William, additional, Datta, S. Deblina, additional, Danner, Robert L., additional, Demirkale, Cumhur Y., additional, and Warner, Sarah, additional

Published
2021
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33. Suspected Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) Reinfections: Incidence, Predictors, and Healthcare Use Among Patients at 238 US Healthcare Facilities, 1 June 2020 to 28 February 2021

Author

Lawandi, Alexander, primary, Warner, Sarah, additional, Sun, Junfeng, additional, Demirkale, Cumhur Y, additional, Danner, Robert L, additional, Klompas, Michael, additional, Gundlapalli, Adi, additional, Datta, Deblina, additional, Harris, Aaron M, additional, Morris, Sapna Bamrah, additional, Natarajan, Pavithra, additional, and Kadri, Sameer S, additional

Published
2021
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34. Neither Blood Culture Positivity nor Time to Positivity Is Associated With Mortality Among Patients Presenting With Severe Manifestations of Sepsis: The FABLED Cohort Study

Author

Paquette, Katryn, primary, Sweet, David, additional, Stenstrom, Robert, additional, Stabler, Sarah N, additional, Lawandi, Alexander, additional, Akhter, Murtaza, additional, Davidson, Adam C, additional, Gavric, Marko, additional, Jinah, Rehman, additional, Saeed, Zahid, additional, Demir, Koray, additional, Sangsari, Sassan, additional, Huang, Kelly, additional, Mahpour, Amirali, additional, Shamatutu, Chris, additional, Caya, Chelsea, additional, Troquet, Jean-Marc, additional, Clark, Greg, additional, Wong, Titus, additional, Yansouni, Cedric P, additional, and Cheng, Matthew P, additional

Published
2021
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41. Reply to Volpicelli et al

Author

Cheng, Matthew P, primary, Lawandi, Alexander, additional, Butler-Laporte, Guillaume, additional, De l’Étoile-Morel, Samuel, additional, Paquette, Katryn, additional, and Lee, Todd C, additional

Published
2020
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42. Real-world Time to Positivity of 2 Widely Used Commercial Blood Culture Systems in Patients With Severe Manifestations of Sepsis: An Analysis of the FABLED Study

Author

Butler-Laporte, Guillaume, primary, Yansouni, Cedric P, additional, Paquette, Katryn, additional, Lawandi, Alexander, additional, Stabler, Sarah N, additional, Akhter, Murtaza, additional, Davidson, Adam C, additional, Gavric, Marko, additional, Jinah, Rehman, additional, Saeed, Zahid, additional, Demir, Koray, additional, Sangsari, Sassan, additional, Huang, Kelly, additional, Mahpour, Amirali, additional, Shamatutu, Chris, additional, Caya, Chelsea, additional, Troquet, Jean-Marc, additional, Clark, Greg, additional, Wong, Titus, additional, Lee, Todd C, additional, Stenstrom, Robert, additional, Sweet, David, additional, and Cheng, Matthew P, additional

Published
2020
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44. Suspected Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) Reinfections: Incidence, Predictors, and Healthcare Use Among Patients at 238 US Healthcare Facilities, 1 June 2020 to 28 February 2021.

Author

Lawandi, Alexander, Warner, Sarah, Sun, Junfeng, Demirkale, Cumhur Y, Danner, Robert L, Klompas, Michael, Gundlapalli, Adi, Datta, Deblina, Harris, Aaron M, Morris, Sapna Bamrah, Natarajan, Pavithra, and Kadri, Sameer S

Subjects
*HEALTH facilities, *REINFECTION, *RETROSPECTIVE studies, *SEVERITY of illness index, *MEDICAL care use, *LONGITUDINAL method, *DISEASE risk factors
Abstract

In a retrospective cohort study, among 131 773 patients with previous coronavirus disease 2019 (COVID-19), reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was suspected in 253 patients (0.2%) at 238 US healthcare facilities between 1 June 2020 and 28 February 2021. Women displayed a higher cumulative reinfection risk. Healthcare burden and illness severity were similar between index and reinfection encounters. [ABSTRACT FROM AUTHOR]

Published
2022
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46. 847. The Effect of Antimicrobial Administration on Blood Culture Positivity in Patients with Severe Manifestations of Sepsis

Author

Cheng, Matthew P, primary, Stenstrom, Robert, additional, Paquette, Katryn, additional, Stabler, Sarah, additional, Akhter, Murtaza, additional, Davidson, Adam, additional, Gavric, Marko, additional, Lawandi, Alexander, additional, Jinah, Rehman, additional, Saheed, Zahid, additional, Demir, Koray, additional, Huang, Kelly, additional, Mahpour, Amirali, additional, Shamatutu, Chris, additional, Caya, Chelsea, additional, Troquet, Jean-Marc, additional, Clark, Greg, additional, Yansouni, Cedric, additional, and Sweet, David, additional

Published
2019
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