engleski

Synergistic activity of fosfomycin in combination with antipseudomonal antibiotics against clinical isolates of Pseudomonas aeruginosa with various resistance phenotypes

Pseudomonas aeruginosa is a leading cause of nosocomial infections, which can be particularly severe in immunocompromised patients. Therapy is often challenging due to intrinsic and acquired resistance. Fosfomycin synergy with other antibiotics has already been assessed in studies, with rates depending on the antibiotic and method used. In this study 51 P. aeruginosa clinical isolates were tested for synergy, ). There were 33, 3% (n=17) multidrug-resistant (MDR) and 54, 9% (n=28) extensively drug-resistant (XDR) isolates. Minimum inhibitory concentrations were determined by broth dilution test. Production of carbapenemases was detected by modified Hodge and CIM test. Isolates exhibiting positive phenotypic tests were subjected to PCR for detection of metallo-beta- lactamases. Synergy was assessed by gradient diffusion strips cross (GDC) and time kill method. The rate of susceptibility to fosfomycin was 47, 1% (n=24). The rates of susceptibility to other antibiotics were as follows: colistin 88, 2% (n=45), amikacin 43, 1% (n=22), piperacillin tazobactam 39, 2% (n=20), ciprofloxacin 21, 6% (n=11), cefepime 19, 6% (n=10), meropenem 19, 6% (n=10), gentamicin 17, 6% (n=9), imipenem 13, 7% (n=7), ceftazidime 11, 8% (n=6). In total 54, 9% (28/51) isolates had a positive modified Hodge and CIM test indicating production of carbapenemases. There were 58, 8% (30/51) isolates demonstrating positive combined disk test with EDTA test indicating the presence of MBL Using the GDC method, the highest rate of synergy as well as the greatest additive effect was observed for combination with ceftazidime (21, 6% and 43, 1% respectively) and gentamicin ( 17, 7% and 43, 1% respectively). ). High rates of indifference were observed in combination with colistin (88, 24%, n=45). Antagonism was not observed in this study. The XDR isolate P. aeruginosa P. 14 positive for VIM-2 did not show any significant differences in the time kill kinetics between any of the tested antibiotics alone and in combination with fosfomycin. Neither synergistic nor antagonistic interactions were noticed. Moreover, no bactericidal effect was observed (Figure 1). On the other hand P. aeruginosa P32 with MDR phenotype and without carbapenemase, showed a reduction of >2log10 CFU / ml after 24h for combinations including colistin, amikacin, piperacillin/tazobactam, gentamicin and ceftazidime compared to each single antibiotic, indicating synergy as shown in Figure 2.. Our findings indicate that based on in vitro testing fosfomycin combination therapy may be a valuable treatment alternative.In our study synergy of fosfomycin with other antibiotics appears to be strain dependent, related to the specific properties of a particular strain and dependent on the method used.

fosfomycin ; resistance ; Pseudomonas aeruginosa ; synergy

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