Abstract
Introduction: Over the past few decades, Klebsiella pneumoniae strains increased their pathogenicity and antibiotic resistance, thereby becoming a major therapeutic challenge. One of the few available therapeutic options seems to be intravenous fosfomycin. Unfortunately, the determination of sensitivity to fosfomycin performed in hospital laboratories can pose a significant problem. Therefore, the aim of the present research was to evaluate the activity of fosfomycin against clinical, multidrug-resistant Klebsiella pneumoniae strains isolated from nosocomial infections between 2011 and 2020, as well as to evaluate the methods routinely used in hospital laboratories to assess bacterial susceptibility to this antibiotic. Materials and Methods: 43 multidrug-resistant Klebsiella strains isolates from various infections were tested. All the strains had ESBL enzymes, and 20 also showed the presence of carbapenemases. Susceptibility was determined using the diffusion method (E-test) and the automated system (Phoenix), which were compared with the reference method (agar dilution). Results: For the reference method and for the E-test, the percentage of strains sensitive to fosfomycin was 65%. For the Phoenix system, the percentage of susceptible strains was slightly higher and stood at 72%. The percentage of fosfomycin-resistant strains in the Klebsiella carbapenemase-producing group was higher (45% for the reference method and E-test and 40% for the Phoenix method) than in carbapenemase-negative strains (25%, 25%, and 20%, respectively). Full (100%) susceptibility categorical agreement was achieved for the E-test and the reference method. Agreement between the automated Phoenix system and the reference method reached 86%. Conclusions: Fosfomycin appears to be the antibiotic with a potential for use in the treatment of infections with multidrug-resistant Klebsiella strains. Susceptibility to this drug is exhibited by some strains, which are resistant to colistin and carbapenems. The E-test, unlike the Phoenix method, can be an alternative to the reference method in the routine determination of fosfomycin susceptibility, as it shows agreement in terms of sensitivity categories and only slight differences in MIC values. The Phoenix system, in comparison to the reference method, shows large discrepancies in the MIC values and in the susceptibility category.
Highlights
Fosfomycin, a natural bactericidal antibiotic and a derivative of phosphoric acid, has been used worldwide for more than 40 years
The antibiograms obtained using the automated BD Phoenix system showed that the tested strains were highly resistant to routinely used antibiotics
Differences were noted in susceptibility to carbapenems, which correlated with the production by the tested strains of carbapenemases, some carbapenemase-negative bacilli showed reduced susceptibility or resistance to these antibiotics, especially ertapenem
Summary
Fosfomycin, a natural bactericidal antibiotic and a derivative of phosphoric acid, has been used worldwide for more than 40 years. Fosfomycin is a bactericidal antibiotic whose unique properties are owed, among other things, to its mechanism of action It is involved in inhibiting cell wall synthesis, but in a different way than in the case of β-lactam or glycopeptide antibiotics. I.v. fosfomycin, which has the smallest hydrophilic molecule among all antibiotics, has good pharmacokinetic properties, including excellent distribution to many tissues This antibiotic achieves clinically relevant concentrations in the serum (does not bind with plasma proteins), kidneys, lungs, bones, heart valves, bladder, prostate gland, and seminal glands. It penetrates the placenta, as well as the blood-brain barrier, reaching high concentrations in the cerebrospinal fluid. Fosfomycin’s effective penetration into bacterial biofilm was confirmed, in particular into the biofilm produced by the Pseudomonas aeruginosa and Staphylococcus aureus strains [7,8]
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