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1.
Int J Antimicrob Agents ; 64(2): 107220, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38810939

ABSTRACT

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.

2.
Environ Sci Pollut Res Int ; 26(33): 34622-34632, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31654308

ABSTRACT

Organophosphorus pesticides are effective, cheap, and used extensively but can harm aquatic organism and human health. Here, water quality criteria (WQCs) for dichlorvos (DDVP) and malathion (MAL) were derived. Nine aquatic organisms native to China were used in toxicity tests. Published toxicity data for aquatic organisms native and non-native to China were also analyzed. DDVP and MAL WQCs were derived using (log-normal model) species sensitivity distributions. Species sensitivity distribution curves indicated native and non-native species have different sensitivities to DDVP. The sensitivities of native and non-native species to MAL were not different because non-native species data for fewer than eight genera were available, so further research is required. The results indicated that native species need to be considered when deriving WQCs. The criteria maximum concentration (CMC) and criteria continuous concentration (CCC) were 1.33 and 0.132 µg/L, respectively, for DDVP, and 0.100 and 0.008 µg/L, respectively, for MAL. The CMCs for DDVP and MAL derived using ETX 2.0 software and species sensitivity ranks were different from the CMCs obtained using the SSD method because of parameter uncertainties. The DDVP and MAL WQCs were significantly lower than Chinese surface water quality standard thresholds. The results provide basic data for revising these thresholds.


Subject(s)
Dichlorvos/analysis , Malathion/analysis , Pesticides/analysis , Water Pollutants, Chemical/analysis , Water Quality/standards , Animals , Aquatic Organisms , China , Humans , Toxicity Tests
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