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Article ; Online: Oral stepdown in Gram-positive bloodstream infections: A step in the right direction.

Caniff, Kaylee E / Rebold, Nicholas / Rybak, Michael J

2023 Volume 43, Issue 3, Page(s) 247–256

Abstract: Bloodstream infections (BSIs) due to Gram-positive organisms have traditionally been treated with prolonged courses of intravenous antimicrobials. However, this dogma is associated with substantial burden to the patient and health care system. ... ...

Abstract	Bloodstream infections (BSIs) due to Gram-positive organisms have traditionally been treated with prolonged courses of intravenous antimicrobials. However, this dogma is associated with substantial burden to the patient and health care system. Consequently, there is growing interest in the utilization of oral stepdown therapy, defined as the transition of intravenous therapy to an active oral agent, for this indication. This review highlights available literature examining oral stepdown in adult patients with BSI due to commonly encountered Gram-positive pathogens, including Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. Support for oral stepdown in this setting is primarily derived from observational studies subject to selection bias. Nevertheless, this treatment strategy exhibits promising potential in carefully selected patients as it is consistently associated with reductions in hospital length of stay without jeopardizing clinical cure or survivability. Prospective, randomized trials are needed for validation of oral stepdown in Gram-positive BSI and to identify the optimal patient population and regimen.
MeSH term(s)	Adult ; Humans ; Bacteremia/drug therapy ; Prospective Studies ; Sepsis/drug therapy ; Staphylococcal Infections/drug therapy ; Staphylococcus aureus ; Anti-Bacterial Agents/therapeutic use
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603158-4
ISSN	1875-9114 ; 0277-0008
ISSN (online)	1875-9114
ISSN	0277-0008
DOI	10.1002/phar.2775
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Article ; Online: Updates in pulmonary drug-resistant tuberculosis pharmacotherapy: A focus on BPaL and BPaLM.

Holger, Dana J / Althubyani, Ali / Morrisette, Taylor / Rebold, Nicholas / Tailor, Marylee

Pharmacotherapy

2024 Volume 44, Issue 3, Page(s) 268–282

Abstract: Drug-resistant tuberculosis (TB) is a major public health concern and contributes to high morbidity and mortality. New evidence supports the use of shorter duration, all-oral regimens, which represent an encouraging treatment strategy for drug-resistant ... ...

Abstract	Drug-resistant tuberculosis (TB) is a major public health concern and contributes to high morbidity and mortality. New evidence supports the use of shorter duration, all-oral regimens, which represent an encouraging treatment strategy for drug-resistant TB. As a result, the landscape of drug-resistant TB pharmacotherapy has drastically evolved regarding treatment principles and preferred agents. This narrative review focuses on the key updates of drug-resistant TB treatment, including the use of short-duration all-oral regimens, while calling attention to current gaps in knowledge that may be addressed in future observational studies.
MeSH term(s)	Humans ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Mycobacterium tuberculosis ; Tuberculosis, Multidrug-Resistant/drug therapy ; Lung
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603158-4
ISSN	1875-9114 ; 0277-0008
ISSN (online)	1875-9114
ISSN	0277-0008
DOI	10.1002/phar.2909
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Article ; Online: Panacea or oversimplification: Relating AUC and troughs.

Rebold, Nicholas / Lodise, Thomas / Rybak, Michael J

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists

2022 Volume 79, Issue 12, Page(s) 1019–1021

MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Area Under Curve ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests ; Retrospective Studies ; Staphylococcal Infections/drug therapy ; Vancomycin
Chemical Substances	Anti-Bacterial Agents ; Vancomycin (6Q205EH1VU)
Language	English
Publishing date	2022-02-08
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1224627-x
ISSN	1535-2900 ; 1079-2082
ISSN (online)	1535-2900
ISSN	1079-2082
DOI	10.1093/ajhp/zxac031
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Article: COVID-19: Before the Fall, An Evidence-Based Narrative Review of Treatment Options.

Rebold, Nicholas / Holger, Dana / Alosaimy, Sara / Morrisette, Taylor / Rybak, Michael

Infectious diseases and therapy

2021 Volume 10, Issue 1, Page(s) 93–113

Abstract: The 2019 novel coronavirus (COVID-19) has quickly become one of the most dire international pandemic crises since the 1918 Spanish flu. Evidence for COVID-19 pharmacological therapies has shown rapid growth and a diverse array of results, but an ... ...

Abstract	The 2019 novel coronavirus (COVID-19) has quickly become one of the most dire international pandemic crises since the 1918 Spanish flu. Evidence for COVID-19 pharmacological therapies has shown rapid growth and a diverse array of results, but an assessment of the value of each piece of evidence must be reinforced. This article aims to review utilized therapies, the evidence level supporting these therapies, as well as drugs under investigation for the treatment of COVID-19. Primary scrutinized therapies include antiviral regimens, such as remdesivir, hydroxychloroquine/chloroquine, lopinavir/ritonavir, immunomodulating drugs, such as corticosteroids and interleukin (IL) inhibitors, and other therapies including convalescent plasma. Only one therapy, dexamethasone, has shown a mortality benefit in randomized controlled trials and summarized evidence for other therapies show limited positive results. Reviewing these therapies in a historical way shows how limited evidence can drive therapy decisions. A broad summary of available evidence can assist clinicians in a return to hierarchical assessments of evidence which can lead to safer patient outcomes, improved distribution of resources, and better targets for appropriate therapy decisions.
Language	English
Publishing date	2021-01-25
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-021-00399-6
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Article: Therapeutic Strategies for Emerging Multidrug-Resistant Pseudomonas aeruginosa.

Kunz Coyne, Ashlan J / El Ghali, Amer / Holger, Dana / Rebold, Nicholas / Rybak, Michael J

Infectious diseases and therapy

2022 Volume 11, Issue 2, Page(s) 661–682

Abstract: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates are frequent causes of serious nosocomial infections that may compromise the selection of antimicrobial therapy. The goal of this review is to summarize recent ...

Abstract	Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates are frequent causes of serious nosocomial infections that may compromise the selection of antimicrobial therapy. The goal of this review is to summarize recent epidemiologic, microbiologic, and clinical data pertinent to the therapeutic management of patients with infections caused by MDR/XDR-P. aeruginosa. Historically, conventional antipseudomonal β-lactam antibiotics have been used for the empiric treatment of MDR/XDR-P. aeruginosa. Owing to the remarkable capacity of P. aeruginosa to confer resistance via multiple mechanisms, these traditional therapies are often rendered ineffective. To increase the likelihood of administering empiric antipseudomonal therapy with in vitro activity, a second agent from a different antibiotic class is often administered concomitantly with a traditional antipseudomonal β-lactam. However, combination therapy may pose an increased risk of antibiotic toxicity and secondary infection, notably, Clostridioides difficile. Multiple novel agents that demonstrate in vitro activity against MDR-P. aeruginosa (e.g., β-lactam/β-lactamase inhibitor combinations and cefiderocol) have been recently granted US Food and Drug Administration (FDA) approval and are promising additions to the antipseudomonal armamentarium. Even so, comparative clinical data pertaining to these novel agents is sparse, and concerns surrounding the scarcity of antibiotics active against refractory MDR/XDR-P. aeruginosa necessitates continued assessment of alternative therapies. This is particularly important in patients with cystic fibrosis (CF) who may be chronically colonized and suffer from recurrent infections and disease exacerbations due in part to limited efficacious antipseudomonal agents. Bacteriophages represent a promising candidate for combatting recurrent and refractory infections with their ability to target specific host bacteria and circumvent traditional mechanisms of antibiotic resistance seen in MDR/XDR-P. aeruginosa. Future goals for the management of these infections include increased comparator clinical data of novel agents to determine in what scenario certain agents may be preferred over others. Until then, appropriate treatment of these infections requires a thorough evaluation of patient- and infection-specific factors to guide empiric and definitive therapeutic decisions.
Language	English
Publishing date	2022-02-12
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-022-00591-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production.

Kunz Coyne, Ashlan J / El Ghali, Amer / Lucas, Kristen / Witucki, Paige / Rebold, Nicholas / Holger, Dana J / Veve, Michael P / Rybak, Michael J

Open forum infectious diseases

2023 Volume 10, Issue 3, Page(s) ofad034

Abstract: Background: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) ... ...

Abstract	Background: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. Methods: This was a retrospective cohort study of hospitalized patients with Results: Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score >4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89). Conclusions: Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy.
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad034
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Article ; Online: Risk Factors for Carbapenem-Resistant

Rebold, Nicholas / Lagnf, Abdalhamid M / Alosaimy, Sara / Holger, Dana J / Witucki, Paige / Mannino, Andrew / Dierker, Michelle / Lucas, Kristen / Kunz Coyne, Ashlan J / El Ghali, Amer / Caniff, Kaylee E / Veve, Michael P / Rybak, Michael J

Microbiology spectrum

2023 Volume 11, Issue 1, Page(s) e0264722

Abstract: The Centers for Disease Control and Prevention (CDC) categorized carbapenem- ... ...

Abstract	The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant
MeSH term(s)	Humans ; Adolescent ; Carbapenems/pharmacology ; Carbapenems/therapeutic use ; Retrospective Studies ; Enterobacteriaceae Infections/drug therapy ; Enterobacteriaceae Infections/microbiology ; Anti-Bacterial Agents/adverse effects ; beta-Lactamase Inhibitors ; Treatment Failure ; Risk Factors ; Microbial Sensitivity Tests
Chemical Substances	Carbapenems ; Anti-Bacterial Agents ; beta-Lactamase Inhibitors
Language	English
Publishing date	2023-01-09
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02647-22
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

Rebold, Nicholas / Alosaimy, Sara / Pearson, Jeffrey C / Dionne, Brandon / Taqi, Ahmad / Lagnf, Abdalhamid / Lucas, Kristen / Biagi, Mark / Lombardo, Nicholas / Eudy, Joshua / Anderson, Daniel T / Mahoney, Monica V / Kufel, Wesley D / D'Antonio, Joseph A / Jones, Bruce M / Frens, Jeremy J / Baumeister, Tyler / Geriak, Matthew / Sakoulas, George /

Farmakiotis, Dimitrios / Delaportas, Dino / Larew, Jeremy / Veve, Michael P / Rybak, Michael J

Infectious diseases and therapy

2024 Volume 13, Issue 3, Page(s) 565–579

Abstract: Introduction: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A ... ...

Abstract	Introduction: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. Methods: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. Results: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q Conclusions: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.
Language	English
Publishing date	2024-03-01
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-024-00933-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Impact of Ceftolozane-Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections.

Holger, Dana J / Rebold, Nicholas S / Alosaimy, Sara / Morrisette, Taylor / Lagnf, Abdalhamid / Belza, Ana Christine / Coyne, Ashlan J Kunz / El Ghali, Amer / Veve, Michael P / Rybak, Michael J

Infectious diseases and therapy

2022 Volume 11, Issue 5, Page(s) 1965–1980

Abstract: Introduction: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase ... ...

Abstract	Introduction: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). Methods: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. Results: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3. Conclusion: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.
Language	English
Publishing date	2022-09-01
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-022-00687-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Clinical Characteristics Associated with Bacterial Bloodstream Coinfection in COVID-19.

Rebold, Nicholas / Alosaimy, Sara / Morrisette, Taylor / Holger, Dana / Lagnf, Abdalhamid M / Ansari, Iman / Belza, Ana C / Cheaney, Laura / Hussain, Huzaifa / Herbin, Shelbye R / Abdul-Mutakabbir, Jacinda / Carron, Caitlin / Sandhu, Avnish / Chopra, Teena / Rybak, Michael J

Infectious diseases and therapy

2022 Volume 11, Issue 3, Page(s) 1281–1296

Abstract: Introduction: Inappropriate antibiotic use in COVID-19 is often due to treatment of presumed bacterial coinfection. Predictive factors to distinguish COVID-19 from COVID-19 with bacterial coinfection or bloodstream infection are limited.: Methods: We ...

Abstract	Introduction: Inappropriate antibiotic use in COVID-19 is often due to treatment of presumed bacterial coinfection. Predictive factors to distinguish COVID-19 from COVID-19 with bacterial coinfection or bloodstream infection are limited. Methods: We conducted a retrospective cohort study of 595 COVID-19 patients admitted between March 8, 2020, and April 4, 2020, to describe factors associated with a bacterial bloodstream coinfection (BSI). The primary outcome was any characteristic associated with BSI in COVID-19, with secondary outcomes including 30-day mortality and days of antibiotic therapy (DOT) by antibiotic consumption (DOT/1000 patient-days). Variables of interest were compared between true BSI (n = 25) and all other COVID-19 cases (n = 570). A secondary comparison was performed between positive blood cultures with true BSI (n = 25) and contaminants (n = 33) on antibiotic use. Results: Fever (> 38 °C) (as a COVID-19 symptom) was not different between true BSI (n = 25) and all other COVID-19 patients (n = 570) (p = 0.93), although it was different as a reason for emergency department (ED) admission (p = 0.01). Neurological symptoms (ED reason or COVID-19 symptom) were significantly higher in the true BSI group (p < 0.01, p < 0.01) and were independently associated with true BSI (ED reason: OR = 3.27, p < 0.01; COVID-19 symptom: OR = 2.69, p = 0.03) on multivariate logistic regression. High (15-19.9 × 10 Conclusion: True BSI in COVID-19 was associated with neurological symptoms and nonsignificant higher WBC, and led to overall higher 30-day mortality and worse patient outcomes.
Language	English
Publishing date	2022-05-11
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2701611-0
ISSN	2193-6382 ; 2193-8229
ISSN (online)	2193-6382
ISSN	2193-8229
DOI	10.1007/s40121-022-00636-6
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