Vancomycin‐Resistant Enterococcal Urinary Tract Infections

Heintz, Brett H.; Halilovic, Jenana; Christensen, Cinda

doi:10.1592/phco.30.11.1136

Cited by 79 publications

(68 citation statements)

References 71 publications

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“…A recent case series of fosfomycin outcomes in complex urinary tract infections due to multidrug-resistant organisms, including VRE, reported that urinary stents were associated with microbiologic failure in fosfomycin monotherapy (3). In order to effectively treat such infections, early hardware removal and complex antimicrobial therapy are often required (9). Based on our findings, combination therapy with fosfomycin and either daptomycin or amoxicillin is highly synergistic and results in enhanced bactericidal activity compared to fosfomycin alone against VRE.…”

supporting

confidence: 55%

“…The antibacterial activity of fosfomycin increased from low to high concentrations but still remained bacteriostatic up to 16ϫ the MIC. Although fosfomycin concentrations are high at this exposure (1,024 to 2,048 g/ml), they represent concentrations comparable to those achieved in the urine of patients after a single 3-g oral dose (9). Interestingly, low exposures of fosfomycin (0.5ϫ the MIC) in combination with daptomycin, amoxicillin, or linezolid produced greater bacterial killing than high concentrations of fosfomycin alone (1 to 16ϫ the MIC) and bacterial killing similar to that induced by high fosfomycin exposures in combination with 0.5ϫ the MICs of secondary antibiotics.…”

mentioning

confidence: 65%

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Fosfomycin Synergy In Vitro with Amoxicillin, Daptomycin, and Linezolid against Vancomycin-Resistant Enterococcus faecium from Renal Transplant Patients with Infected Urinary Stents

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Jorgenson

Wergin

et al. 2013

Antimicrob Agents Chemother

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bFosfomycin is a potential option for vancomycin-resistant enterococcus (VRE) infections despite limited in vitro and clinical data. In this study, 32 VRE isolates from renal transplant patients with urinary stent infections were susceptible to fosfomycin, daptomycin, and linezolid and resistant to amoxicillin, minocycline, and nitrofurantoin based on their MIC 50 s and MIC 90 s. Fosfomycin was bacteriostatic at 0.5 to 16؋ the MIC (32 to 2,048 g/ml); synergy occurred when fosfomycin was combined with daptomycin (2.8 to 3.9 log 10 CFU/ml kill; P < 0.001) or amoxicillin (2.6 to 3.4; P < 0.05). These combinations may be potent options to treat VRE urinary infections pending investigation of clinical efficacy. Solid-organ transplant recipients are at increased risk for colonization with vancomycin-resistant enterococcus (VRE) and vulnerable to active infections with this organism (1). At our institution, a 7-French, 16-cm double-J stent is inserted through the ureter into the renal pelvis and then into the bladder at the time of kidney transplantation. Biofilm development often precipitates colonization of the stents and results in sequestered, stationaryphase bacteria that further resist the effects of antibiotics.Fosfomycin, a phosphonic acid derivative initially isolated in 1969 from cultures of Streptomyces species, is an oral therapy for uncomplicated urinary tract infections (UTIs) (2). It is often bactericidal against multidrug-resistant Gram-positive and Gramnegative pathogens, although it has not been well studied against VRE. The antibacterial activity of fosfomycin is achieved by inhibiting the enzyme N-acetylglucosamine (UDP-GlcNAc) enolpyruvyl transferase (MurA), which synthesizes UDP-N-acetylenolpyruvylglucosamine, an essential component in the biosynthesis of peptidoglycan (2). It is highly concentrated in the urine, with peak values of 1,053 to 4,415 g/ml within 4 h after a single oral 3-g dose (2). Fosfomycin has gained recent interest as a potential therapeutic option for treating infections caused by VRE despite limited efficacy data (3).The aim of this study was to investigate fosfomycin activity in vitro alone and in combination with other antibiotic treatment options against VRE urine isolates collected from renal transplant patients with urinary stent infections. We present synergistic combinations with fosfomycin that may be useful treatment options for these situations.(Portions of this work were presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2011 [4].) Thirty-two VRE (Enterococcus faecium) isolates were collected from renal transplant patients with urinary stent infections from 2007 to 2010 at a tertiary medical center. Enterococcus faecalis ATCC 29212 was used as a control strain. The antibiotics evaluated were amoxicillin, fosfomycin, nitrofurantoin, and minocycline, purchased from Sigma-Aldrich (St. Louis, MO), as well as linezolid (Pfizer, NY) and daptomycin (Cubist, Lexington, MA), which were commercially purchased.Antibiotic activi...

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supporting

confidence: 55%

mentioning

confidence: 65%

Fosfomycin Synergy In Vitro with Amoxicillin, Daptomycin, and Linezolid against Vancomycin-Resistant Enterococcus faecium from Renal Transplant Patients with Infected Urinary Stents

Descourouez

Jorgenson

Wergin

et al. 2013

Antimicrob Agents Chemother

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“…Patients with severe infections often have multisystem organ failure requiring renal replacement therapy, and continuous therapies are frequently preferred over intermittent hemodialysis in intensive care patients to avoid the development or exacerbation of hypotension and maximize fluid removal. Current dosing recommendations for piperacillin-tazobactam in patients receiving continuous renal replacement therapy (CRRT) (1,2) originate from either pharmacokinetic estimates or studies with relatively few patients and lower doses of CRRT than are used today (3,4). We designed this multicenter prospective observational study to evaluate the pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in patients receiving CRRT with contemporary dialysis equipment and prescriptions.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT

Bauer¹,

Salem

Connor

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today. This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions.Design, setting, participants, & measurements A multicenter prospective observational study in the intensive care units of two academic medical centers was performed, enrolling patients with AKI or ESRD receiving piperacillin-tazobactam while being treated with continuous renal replacement therapy. Pregnant women, children, and patients with end stage liver disease were excluded from enrollment. Plasma and continuous renal replacement therapy effluent samples were analyzed for piperacillin and tazobactam levels using HPLC. Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations. Multivariate analyses were used to examine the association of patient and continuous renal replacement therapy characteristics with piperacillin pharmacokinetic parameters.Results Forty-two of fifty-five subjects enrolled had complete sampling. Volume of distribution (median=0.38 L/kg, intraquartile range=0.20 L/kg) and elimination rate constants (median=0.104 h 21 , intraquartile range=0.052 h 21 ) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters. Probability of target attainment for piperacillin was 83% for total drug but only 77% when the unbound fraction was considered.Conclusions There is significant patient to patient variability in pharmacokinetic/pharmacodynamic parameters in patients receiving continuous renal replacement therapy. Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy.

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“…This bacterium, is known by its natural resistance to some antibiotics; large (Arias and Murray, 2012;Heintz et al, 2010;Sartelli, 2010). The biogenesis and biofilm formation ability also contribute to the treatment of infections caused by E. faecalis.…”

Section: Introductionmentioning

confidence: 99%

Relationship between the probiotic Lactobacillus rhamnosus and Enterococcus faecalis during the biofilm formation

Montecinos¹,

Jofre²,

Amêndola³

et al. 2016

Afr. J. Microbiol. Res.

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One of the factors that make the treatment of Enterococcus faecalis infections difficult is their ability to form biofilm, as well as their natural and acquired resistance to antibiotics which does not have specific drugs for their inhibition. This fact makes essential the search for alternative treatments, as the use of probiotics strains of Lactobacillus rhamnosus has been effective in the treatment of some diseases. In this investigation, the relationship between the probiotic strain of L. rhamnosus and E. faecalis during the biofilm formation was analyzed. Standardized suspensions used in biofilm development and treatment in different stages of the biofilm formation were prepared. The L. rhamnosus suspension was placed in contact for 90 min with E. faecalis freshly created biofilms (initial adherence) in the 24 h biofilms. The same was made with E. faecalis suspension on L. rhamnosus biofilms. L. rhamnosus showed no inhibitory effects on E. faecalis biofilms formation, with an increase in the counting of colony forming units in the treated groups (p=0.0047, p=0.0060). About the L. rhamnosus biofilms, there was no significant difference for both treatment stages. The probiotic strain interfered in vitro with the E. faecalis biofilm formation, thereby intensifying the growth of E. faecalis biofilm.

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Vancomycin‐Resistant Enterococcal Urinary Tract Infections

Cited by 79 publications

References 71 publications

Fosfomycin Synergy In Vitro with Amoxicillin, Daptomycin, and Linezolid against Vancomycin-Resistant Enterococcus faecium from Renal Transplant Patients with Infected Urinary Stents

Fosfomycin Synergy In Vitro with Amoxicillin, Daptomycin, and Linezolid against Vancomycin-Resistant Enterococcus faecium from Renal Transplant Patients with Infected Urinary Stents

Pharmacokinetics and Pharmacodynamics of Piperacillin-Tazobactam in 42 Patients Treated with Concomitant CRRT

Relationship between the probiotic Lactobacillus rhamnosus and Enterococcus faecalis during the biofilm formation

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