Fosfomycin-ampicillin versus gentamicin-ampicillin in the treatment of critically Ill patients with pneumonia

Nissen, Lorenzo; Jacobsen, John R.; Ravn, T.; Wahlgreen, Claus; Auning-Hansen, H

doi:10.1007/bf01644272

Cited by 17 publications

(8 citation statements)

References 9 publications

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“…No new safety concerns were identified during this study. The adverse events observed in this study were similar to those seen in other studies of healthy subjects and across the decades of clinical experience with fosfomycin (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Discussionsupporting

confidence: 85%

Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers

Wenzler

Ellis-Grosse

Rodvold

2017

Antimicrob Agents Chemother

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The pharmacokinetics, safety, and tolerability of intravenous (i.v.) fosfomycin disodium (ZTI-01) and oral fosfomycin tromethamine were evaluated after a single dose in 28 healthy adult subjects. Subjects received a single 1-h i.v. infusion of 1 g and 8 g fosfomycin disodium and a single dose of 3 g oral fosfomycin tromethamine in a phase I, randomized, open-label, three-period crossover study. Serial blood and urine samples were collected before and up to 48 h after dosing. The mean pharmacokinetic parameters Ϯ standard deviations of fosfomycin in plasma after 1 g and 8 g i.v., respectively, were the following: maximum clearance of drug in serum (C max ), 44.3 Ϯ 7.6 and 370 Ϯ 61.9 g/ml; time to maximum concentration of drug in serum (T max ), 1.1 Ϯ 0.05 and 1.08 Ϯ 0.01 h; volume of distribution (V), 29.7 Ϯ 5.7 and 31.5 Ϯ 10.4 liters; clearance (CL), 8.7 Ϯ 1.7 and 7.8 Ϯ 1.4 liters/h; renal clearance (CL R ), 6.6 Ϯ 1.9 and 6.3 Ϯ 1.6 liters/h; area under the concentrationtime curve from 0 to infinity (AUC 0 -∞ ), 120 Ϯ 28.5 and 1,060 Ϯ 192 g·h/ml; and half-life (t 1/2 ), 2.4 Ϯ 0.4 and 2.8 Ϯ 0.6 h. After oral administration, the parameters were the following: C max , 26.8 Ϯ 6.4 g/ml; T max , 2.25 Ϯ 0.4 h; V/F, 204 Ϯ 70.7 liters; CL/F, 17 Ϯ 4.7 liters/h; CL R , 6.5 Ϯ 1.8 liters/h; AUC 0 -∞ , 191 Ϯ 57.6 g · h/ml; and t 1/2 , 9.04 Ϯ 4.5 h. The percent relative bioavailability of orally administered fosfomycin was 52.8% in relation to the 1-g i.v. dose. Approximately 74% and 80% of the 1-g and 8-g i.v. doses were excreted unchanged in the urine by 48 h compared to 37% after oral administration, with the majority of this excretion occurring by 12 h regardless of dosage form. No new safety concerns were identified during this study. The results of this study support further investigation of i.v. fosfomycin in the target patient population, including patients with complicated urinary tract infections and pyelonephritis.

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Section: Discussionsupporting

confidence: 85%

Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers

Wenzler

Ellis-Grosse

Rodvold

2017

Antimicrob Agents Chemother

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“…Seven trials were randomized controlled trials [ 10 , 12 – 17 ] and one was a retrospective study [ 11 ]. Fosfomycin was used for the treatment of pneumonia including ventilator-associated pneumonia [ 12 , 17 ], primary bacteremia [ 17 ], complicated intra-abdominal infection, UTI [ 17 ], skin and soft tissue infections [ 17 ], acute hematogenous osteomyelitis in children [ 11 ], prevention of infection after urological surgery [ 13 ], prophylaxis of surgical site infection after elective total knee arthroplasty [ 14 ] and colorectal surgery [ 10 , 15 , 16 ]. Fosfomycin was administered up to 3 weeks at a dose up to 12 g but the majority of patients in these trials (530/664) received fosfomycin for 1–3 days as prophylaxis for surgical site infections.…”

Section: Resultsmentioning

confidence: 99%

Adverse Events Associated with Fosfomycin Use: Review of the Literature and Analyses of the FDA Adverse Event Reporting System Database

et al. 2015

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IntroductionThe growing problem of antibacterial resistance resulted in an increased interest in fosfomycin, especially its parenteral formulation. We reviewed fosfomycin safety profile using the Food and Drug Administration Adverse Event (AE) Reporting System (FAERS) and published literature.MethodsWe conducted a FAERS search and disproportionality analysis of all fosfomycin-associated AEs. We also conducted a FAERS search for AEs implicating fosfomycin as the primary suspect and a search of reports of fosfomycin-associated bone marrow toxicity. We then review the literature for publications reporting AEs associated with fosfomycin by conducting PubMed searches.ResultsThe disproportionality analysis of all FAERS reports of fosfomycin-associated AEs produced a higher than expected frequency of agranulocytosis, liver injury, severe skin reactions, and pseudomembranous colitis. Subsequent search for AEs where fosfomycin was the primary suspect and the literature review did not suggest a higher association of fosfomycin with these AEs. The search of bone marrow toxicity reports did not demonstrate an association between aplastic anemia and fosfomycin. The literature review selected 23 trials of parenteral administration of fosfomycin in 1242 patients including 8 comparative and 15 non-comparative trials. For oral fosfomycin, only prospective comparative trials (n = 28) in 2743 patients were included. The most frequent AEs associated with parenteral fosfomycin included rash, peripheral phlebitis, hypokalemia, and gastrointestinal disorders. Serious AEs such as aplastic anemia, anaphylaxis, and liver toxicities were reported infrequently. Gastrointestinal disorders were the most common AEs associated with oral fosfomycin.ConclusionThe identified AEs were consistent with the safety profile of fosfomycin. No new safety signals related to either parenteral or oral fosfomycin were identified.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-015-0092-8) contains supplementary material, which is available to authorized users.

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“…All studies dealing with the curative use of intravenous fosfomycin in adult patients are presented in Table 1. 33,65,66,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84]…”

Section: Intravenous Fosfomycin In Clinical Usementioning

confidence: 99%

The revival of fosfomycin

Michalopoulos

Livaditis

Gougoutas

2011

International Journal of Infectious Diseases

341

296

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Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969. There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use. Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis in both Gram-positive and Gram-negative bacteria by inhibiting the initial step involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Its unique mechanism of action may provide a synergistic effect to other classes of antibiotics including beta-lactams, aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the treatment of urinary tract infections, particularly those caused by Escherichia coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in combination with other antibiotics for the treatment of nosocomial infections due to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone, cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well tolerated, with a low incidence of adverse events. Further randomized controlled trials are needed in order to evaluate the efficacy of intravenous fosfomycin for the management of nosocomial infections due to MDR pathogens.

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Fosfomycin-ampicillin versus gentamicin-ampicillin in the treatment of critically Ill patients with pneumonia

Cited by 17 publications

References 9 publications

Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers

Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers

Adverse Events Associated with Fosfomycin Use: Review of the Literature and Analyses of the FDA Adverse Event Reporting System Database

The revival of fosfomycin

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