<i>In Vitro</i>
            Interactions of Antimicrobial Combinations with Fosfomycin against KPC-2-Producing Klebsiella pneumoniae and Protection of Resistance Development

Souli, María; Galani, Irene; Boukovalas, Stefanos; Gourgoulis, Michael George; Chryssouli, Zoi; Kanellakopoulou, Kyriaki; Panagea, Theofano; Giamarellou, Helen

doi:10.1128/aac.01086-10

Cited by 97 publications

(69 citation statements)

References 14 publications

(9 reference statements)

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“…A similar approach for reading disk diffusion has been proposed by others (18,29). It can be argued that also from a clinical point of view, it might be appropriate to ignore a certain subpopulation of fosfomycinresistant mutants when reading susceptibility tests, because intravenous fosfomycin is mostly used in combination therapy for infections caused by multidrug-resistant Enterobacteriaceae (5), and combination therapy has been shown to prevent the development of fosfomycin resistance (30). It is an open question as to which fosfomycin susceptibility testing method best predicts treatment outcome.…”

Section: Discussionmentioning

confidence: 99%

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Kaase

Szabados²,

Anders

et al. 2014

J Clin Microbiol

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bDue to the increase in multidrug-resistant Enterobacteriaceae, the interest in older antimicrobial agents, like fosfomycin, has increased. In this study, we used agar dilution for testing susceptibilities to fosfomycin in a collection of 107 carbapenem-nonsusceptible Enterobacteriaceae isolates, of which 80 produced various types of carbapenemases, including KPC, VIM, NDM, and OXA-48. Overall, 78% of the strains had fosfomycin MICs of <32 mg/liter and were thus considered to be susceptible according to the current EUCAST breakpoint. The MIC 50 and MIC 90 were 8 mg/liter and 512 mg/liter, respectively. Escherichia coli strains had significantly lower fosfomycin MICs than the Klebsiella pneumoniae and Enterobacter cloacae strains. Furthermore, comparisons of the susceptibility testing methods, like Etest and disk diffusion, were performed against agar dilution as the reference method. Essential agreement between Etest and agar dilution was 78.9%, and categorical agreement between the two methods was 92.5%, with 20% very major errors and 2.6% major errors. Disk diffusion was studied with 50-g and 200-g fosfomycin disks, but no inhibition zone breakpoint that reduced very major and major errors to an acceptable level was found. Etest and disk diffusion showed poor agreement with fosfomycin agar dilution.

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Section: Discussionmentioning

confidence: 99%

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Kaase

Szabados²,

Anders

et al. 2014

J Clin Microbiol

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“…In clinical practice, combinations of antibiotics are commonly administered to patients with severe infections either empirically to broaden the coverage or definitively for polymicrobial infections (37,38). Evidence derived from clinical and in vitro studies reveals that a combination of antibiotics might prevent the emergence of resistant strains during therapy (39,40). However, clinical data do not clearly support the idea that antibiotic combinations reduce the emergence of resistance (41).…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae: Systematic Evaluation of the Available Evidence

Falagas

Lourida

Poulikakos

et al. 2014

Antimicrob Agents Chemother

321

216

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We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

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“…77 Some in-vitro data suggest synergy in combining two agents against carbapenemase-producing K. pneumoniae, even when the pathogen is resistant to one of these agents. 78,79 Synergy was claimed for a combination of polymyxin B and either rifampin or doxycycline, resulting in at least a four-fold decrease in the MIC of polymyxin B when both drugs were used at physiologically achievable concentrations in one study. 78 In another study a combination of fosfomycin with meropenem or colistin was asserted to be synergistic, based on 100-fold more extensive killing than with the more active single agent.…”

Section: Combination Therapy In Infections Due To Resistant Gram-negamentioning

confidence: 99%

“…78 In another study a combination of fosfomycin with meropenem or colistin was asserted to be synergistic, based on 100-fold more extensive killing than with the more active single agent. 79 Nevertheless there is a profound lack of clarity on when and how the various different measures of synergy used in vitro translate into clinical advantage; moreover there must be a concern about publication bias: studies that detect synergy are more likely to be reported and published than those that fail to do so.…”

Section: Combination Therapy In Infections Due To Resistant Gram-negamentioning

confidence: 99%

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

et al. 2013

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The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various anti-gram-positive agents. Data on the use of these agents in leukemic patients are scanty, with only linezolid subjected to formal trials. The Expert Group of the 4 th European Conference on Infections in Leukemia has developed guidelines for their use in these patient populations. Targeted therapy should be based on (i) in vitro susceptibility data, (ii) knowledge of the best treatment option against the particular species or phenotype of bacteria, (iii) pharmacokinetic/pharmacodynamic data, and (iv) careful assessment of the risk-benefit balance. For infections due to resistant Gram-negative bacteria, these agents should be preferably used in combination with other agents that remain active in vitro, because of suboptimal efficacy (e.g., tigecycline) and the risk of emergent resistance (e.g., fosfomycin). The paucity of new antibacterial drugs in the near future should lead us to limit the use of these drugs to situations where no alternative exists. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o n 2 0 1 3organizing committee and experts were solicited to form the working group. The group reviewed the published English-language literature and prepared proposals on treatment options for infections due to resistant bacteria. Papers for review were sought using PubMed with the terms "linezolid", "daptomycin", "quinupristin/ dalfopristin", "colistin or polymyxin", "tigecycline", "fosfomycin", "telavancin", "ceftaroline" AND "stem cell transplantation or bone marrow transplant or leukemia or hematological malignancy or cancer". References cited in the articles identified were also considered. In respect of 'Duration of therapy', the main search terms used were "antibiotic therapy"; "stem cell transplantation or bone marrow transplantation or hematological malignancy or cancer"; "febrile neutropenia" and "duration therapy", "discontinuation antibiotics" and "microbiologically documented infection". Definitions of resistanceA bacterial isolate was considered non-susceptible if it was categorized resistant, intermediate or non-susceptible when using clinical breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), Clinical and Laboratory Standards Institute (CLSI) or the US Food and Drug Administration (FDA). Definitions of 'MDR' vary among authors and usually presume resistance to at least two antibiotics used in empiric therapy (3 rd 4 th -generation cephalosporins, carbapenems or piperacillin/tazobactam) or resistance to at least three of the following antibiotic classes: antipseudomonal penicillins, cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. [11][12][13][14][15] According to the recent definition of the European Centre for Disease Prevention and Control...

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In Vitro Interactions of Antimicrobial Combinations with Fosfomycin against KPC-2-Producing Klebsiella pneumoniae and Protection of Resistance Development

Cited by 97 publications

References 14 publications

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Antibiotic Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae: Systematic Evaluation of the Available Evidence

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

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