In vivo efficacy of combination of colistin with fosfomycin or minocycline in a mouse model of multidrug-resistant Acinetobacter baumannii pneumonia

Abstract

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.

Phylogenetic group determination and plasmid virulence gene profiles of colistin-resistant Escherichia coli originated from the broiler meat supply chain in Bogor, Indonesia

“…The evolution of E. coli strains is highly determined in the genomic region, and this mechanism [ 5 , 40 , 42 , 43 ]. The virulence APEC genes and the antibiotic-resistant genes are often on the same plasmid [ 44 ], so it potential to be transferred to other E. coli bacteria.…”

Fosfomycin as Partner Drug for Systemic Infection Management. A Systematic Review of Its Synergistic Properties from In Vitro and In Vivo Studies

“…Synergism rates were not unanimous on all studies but was reported in 23/29 papers. Synergisms rate were 100% in 2 in vitro studies against K. pneumoniae [50,71] and 2 in vivo studies respectively against A. baumannii and E.coli [72,73]. The overall effect was indifferent on most isolates of P. aeruginosa and Enterobacterales.…”

Efficacy of a Fosfomycin-Containing Regimen for Treatment of Severe Pneumonia Caused by Multidrug-Resistant Acinetobacter baumannii: A Prospective, Observational Study

“…Combination of carbapenem plus colistin seems to be the first option for treatment of MDR-AB infections [33]. In a recent randomized trial comparing colistin alone versus colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant gramnegative bacteria, the authors concluded that combination therapy was not more efficient than monotherapy and that adding meropenem Many in vitro studies suggested a possible role for intravenous fosfomycin also for the treatment of MDR-AB [13][14][15]. Recently, a fosfomycin-containing regimen showed a more beneficial effect on all-cause mortality, with favorable effectiveness in clinical cure and [16].…”

“…A recent study showed fosfomycin achieved effective concentrations in infected lung tissue [35], and fosfomycin was introduced as a treatment option for infections caused by MDR-AB [36]. In a time-kill study, fosfomycin with colistin showed bactericidal and synergistic effects at 8 h, reducing the bacterial load in the lungs at 48 h compared with monotherapies and the combination of colistin plus minocycline [37]. In another recent study, a combination of colistin and fosfomycin had significantly better microbiologic responses with trends toward more favorable treatment outcomes and lower mortality compared with those treated with colistin alone [38].…”

“…Recently, new agents with microbiologic activity against MDR-AB strains have been developed [ 11 , 12 ]; however, the use of “old” antibiotics for these difficult-to-treat infections is mandatory, and antimicrobial combinations should be carefully evaluated. Many in vitro studies suggested a possible role for intravenous fosfomycin also for the treatment of MDR-AB [ 13 – 15 ]. Recently, a fosfomycin-containing regimen showed a more beneficial effect on all-cause mortality, with favorable effectiveness in clinical cure and microbiologic eradication [ 16 ].…”