Phenotypic Antibiotic Resistance in ZEUS: A Multi-center, Randomized, Double-Blind Phase 2/3 Study of ZTI-01 vs. Piperacillin-Tazobactam (P-T) in the Treatment of Patients with Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP)

Eckburg, Paul B.; Skarinsky, David; Das, Anita; Ellis-Grosse, Evelyn J.

doi:10.1093/ofid/ofx163.1360

Cited by 3 publications

(6 citation statements)

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“…The difference might be explained by the epidemiology, susceptibility, and MIC distributions of fosfomycin against CRE. MICs of fosfomycin against CRE in our study (MIC 90 > 1024 mg/L) were higher than that of the previous studies (MICs 0.5 to >512 mg/L) [36,37]. Additionally, our study showed that most of Enterobacterales clinical isolates were Klebsiella pneumoniae.…”

Section: Discussioncontrasting

confidence: 71%

“…The previous studies demonstrated that the combination therapy of IVFOS with other antibiotics was associated with a reduction of mortality in critically ill patients with CRE infections [34,35]. However, some previous studies showed that IVFOS monotherapy was associated with high clinical cure rate (100%) and microbiological eradication (56%) in patients with acute pyelonephritis caused by CRE [36,37]. The difference might be explained by the epidemiology, susceptibility, and MIC distributions of fosfomycin against CRE.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation

et al. 2020

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There are limited intravenous fosfomycin disodium (IVFOS) dosing regimens to treat carbapenem-resistant Enterobacterales (CRE) infections. This study aimed to use Monte Carlo simulation (MCS) for evaluation of IVFOS dosing regimens in critically ill patients with CRE infections. The dosing regimens in critically ill patients with various creatinine clearance were evaluated with MCS using minimum inhibitory concentration (MIC) distributions of fosfomycin against CRE clinical isolates in Thailand and the 24 h area under the plasma drug concentration–time curve over the minimum inhibitory concentration (AUC0-24/MIC) of ≥21.5 to be a target for IVFOS. The achieved goal of the probability of target attainment (PTA) and a cumulative fraction of response (CFR) were ≥90%. A total of 129 non-duplicated CRE clinical isolates had MIC distributions from 0.38 to >1024 mg/L. IVFOS 8 g every 8 h, 1 h, or 4 h infusion, could achieve approximately 90% PTA of AUC0-24/MIC target to treat CRE infections with MICs ≤ 128 mg/L. According to PTA target, an IVFOS daily dose to treat carbapenem-resistant Escherichia coli based on Clinical Laboratory Standards Institute (CLSI) breakpoints for urinary tract infections and one to treatment for CRE infections based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were 16 g/day and 8 g/day, respectively. All dosing regimens of IVFOS against CRE achieved CFR ≤ 70%. This study proposes the IVFOS dosing regimens based on CLSI and EUCAST breakpoints for the treatment of CRE infections. However, further clinical studies are needed to confirm the results of these findings.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation

et al. 2020

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“…Although few clinical studies evaluating FOS in CI or PI against Gram-positive bacteria are available to-date, this review suggests potential benefits from the use of this antibiotic in this setting [18,19,27,31,32]. This is interesting if we take into consideration the anti-biofilm properties of FOS, against both Gram-positive and Gram-negative bacterial strains [45,46].…”

Section: Discussionmentioning

confidence: 94%

“…Fourteen studies investigated FOS dosing regimens in the setting of Gram-negative bacteria (2 in vivo studies, 8 simulation studies, 4 clinical trials, 1 review [4,[20][21][22][23][24][25][26][27][28][29][30][31][32]), while FOS dosing regimens against Gram-positive bacteria were evaluated in 5 studies (2 in vitro studies, 2 clinical trials, 1 review [18,19,27,31,32]). One study [33] did not evaluate the activity of FOS administered in CI since its objective was to report PK/ PD parameters in healthy volunteers.…”

Section: Resultsmentioning

confidence: 99%

“…FOS monotherapy 16 g per day, administered either as 4 g q6hr PI [28,29] or 8 g q12hr PI [28], resulted active against non-MDR isolates in two studies. Administration of 18 g per day (6 g q8hr PI) was evaluated in a PK model simulation [25] and in the ZEUS trial [31,32]. Finally, dosing regimens of 24 g per day, either as 4 g q4hr PI [23], 6 g q6hr PI [24,26,27], or 8 g q8hr PI [24,[27][28][29], resulted active also against MDR isolates.…”

Section: Resultsmentioning

confidence: 99%

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Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies

Antonello

Bella

Maraolo

et al. 2021

Eur J Clin Microbiol Infect Dis

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Fosfomycin (FOS) administered intravenously has been recently rediscovered for the treatment of systemic infections due to multidrug-resistant bacteria. Its pharmacokinetic properties suggest a time-dependent dosing schedule with more clinical benefits from prolonged (PI) or continuous infusion (CI) than from intermittent infusion. We revised literature concerning PI and CI FOS to identify the best dosing regimen based on current evidence. We performed a MEDLINE/PubMed search. Ninety-one studies and their pertinent references were screened. Seventeen studies were included in the present review. The activity of FOS against Gram-negative and Gram-positive bacteria was evaluated in fourteen and five studies, respectively. Six studies evaluated FOS activity in combination with another antibiotic. Daily dosing of 12, 16, 18 or 24 g, administered with different schedules, were investigated. These regimens resulted active against the tested isolates in most cases. Emergence of resistant isolates has been shown to be preventable through the coadministration of another active antibiotic. FOS is a promising option to treat systemic infections caused by multidrug-resistant bacteria. Coadministration with another active molecule is required to prevent the emergence of resistant bacterial strains. The results of our review suggest that a therapeutic regimen including a loading dose of FOS 8 g followed by a daily dose of 16 g or 24 g CI could be the best therapeutic approach for patients with normal renal function. The dosing regimens in patients with renal insufficiency and CI or PI superiority compared with intermittent infusion in clinical settings should be further investigated.

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Eravacycline, the First and Unique Fluorocycline Antibacterial Agent

Rahman,

Shathi,

Amin

et al. 2024

J Bacteriol Virol.

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in medical history (1). However, antibiotic resistance is becoming a major global health issue (2). Despite the popular notion that antibiotic exposure is limited to the modern "antibiotic era," the researcher has discovered traces of exposed tetracycline in human skeletal remains dating back to 350-550 CE in ancient Sudanese Nubia (1,3,4). Nevertheless, in the modern era, after its discovery in the 1940s, tetracycline has taken a special place because of its antibacterial activity against many life-threatening microorganisms (5,6).Chlortetracycline was the first tetracycline discovered by the American Cyanamide Company in the 1940s and it is a natural tetracycline isolated from Streptomyces aureofaciens (4-6). Its effectiveness against various pathogens, such as Actinomycetes, Escherichia coli, Mycoplasma spp., and Rickettsiae has solidified its place as a key antibiotics in the

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Phenotypic Antibiotic Resistance in ZEUS: A Multi-center, Randomized, Double-Blind Phase 2/3 Study of ZTI-01 vs. Piperacillin-Tazobactam (P-T) in the Treatment of Patients with Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP)

Cited by 3 publications

References 0 publications

Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation

Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation

Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies

Eravacycline, the First and Unique Fluorocycline Antibacterial Agent

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