RESUMO
Some radiological contrast agents have been shown to have effects on bacterial growth. In this study, the antibacterial effect and mechanism of action of iodinated X-ray contrast agents (Ultravist 370, Iopamiro 300, Telebrix Gastro 300 and Visipaque) and complexed lanthanide MRI contrast solutions (MultiHance and Dotarem) were tested against six different microorganisms. Bacteria with high and low concentrations were exposed to media containing different contrast media for various lengths of time and at pH 7.0 and 5.5. The antibacterial effect of the media was examined in further tests using agar disk diffusion analysis and the microdilution inhibition method. Bactericidal effects were found for microorganisms at low concentrations and low pH. Reductions were confirmed for Staphylococcus aureus and Escherichia coli.
Assuntos
Antibacterianos , Meios de Contraste , Meios de Contraste/farmacologia , Projetos Piloto , Raios X , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Escherichia coli , Imageamento por Ressonância MagnéticaRESUMO
New therapeutic strategies are needed to combat the emergence of infections due to multidrug-resistant Neisseria gonorrhoeae. In this study, fosfomycin (FOS) was tested against 89 N. gonorrhoeae isolates using the Etest method, showing MIC50/MIC90s of only 8/16 µg/ml (range, ≤1 to 32 µg/ml). FOS in combination with ceftriaxone (CRO) or azithromycin (AZT) was then evaluated using the checkerboard method for eight strains, including N. gonorrhoeae F89 (CRO-resistant) and AZT-HLR (high-level AZT-resistant). All combinations that included FOS gave indifferent effects (fractional inhibitory concentration [FIC] index values, 1.2 to 2.3 for FOS plus CRO, 1.8 to 3.2 for FOS plus AZT). Time-kill experiments for FOS, CRO, AZT, and their combinations (at 0.5×, 1×, 2×, and 4× the MIC) were performed against N. gonorrhoeae strain ATCC 49226, one N. gonorrhoeae multiantigen sequence typing (NG-MAST) sequence type 1407 (ST1407) strain, F89, and AZT-HLR. For all strains, at 24 h, the results indicated that (i) FOS was bactericidal at 2× the MIC, but after >24 h, there was regrowth of bacteria; (ii) CRO was bactericidal at 0.5× the MIC; (iii) AZT was bactericidal at 4× the MIC; (iv) CRO plus AZT was less bactericidal than was CRO alone; (v) FOS plus AZT was bactericidal at 2× the MIC; and (vi) CRO plus AZT and FOS plus CRO were both bactericidal at 0.5× the MIC, but FOS plus CRO had more rapid effects. FOS is appealing for use in the management of N. gonorrhoeae infections because of its single and oral formulation. However, our results suggest it be used in combination with CRO. After the appropriate clinical trials are conducted, this strategy could be implemented for the treatment of infections due to isolates possessing resistance to CRO and/or AZT.
Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Fosfomicina/farmacologia , Neisseria gonorrhoeae/efeitos dos fármacos , Quimioterapia Combinada/métodos , Gonorreia/tratamento farmacológico , Gonorreia/microbiologia , Humanos , Testes de Sensibilidade Microbiana/métodosRESUMO
BACKGROUND: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce. METHODS: We compared the characteristics of Ng detected during 1998-2001 (n = 26) to those detected during 2009-2012 (n = 34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed. RESULTS: The following susceptibility results were obtained (period: % of non-S, MIC90 in mg/L): penicillin (1998-2001: 42.3%, 3; 2009-2012: 85.3%, 16), cefixime (1998-2001: 0%, ≤0.016; 2009-2012: 8.8%, 0.125), ceftriaxone (1998-2001: 0%, 0.004; 2009-2012: 0%, 0.047), ciprofloxacin (1998-2001: 7.7%, 0.006; 2009-2012: 73.5%, ≥32), azithromycin (1998-2001: 11.5%, 0.25; 2009-2012: 23.6%, 0.38), tetracycline (1998-2001: 65.4%, 12; 2009-2012: 88.2%, 24), spectinomycin (1998-2001: 0%, 12; 2009-2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998-2001 to 70.6% in 2009-2012. International STs and genogroups (G) emerged during 2009-2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion). CONCLUSIONS: The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla , Gonorreia/tratamento farmacológico , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Adolescente , Adulto , Azitromicina , Cefixima/farmacologia , Ceftriaxona/farmacologia , Criança , Pré-Escolar , Ciprofloxacina/farmacologia , Feminino , Gonorreia/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Penicilinas/farmacologia , Fenótipo , Suíça/epidemiologia , Tetraciclina/farmacologia , Adulto JovemRESUMO
Aerococcus urinae can cause severe infections (bacteraemia and endocarditis) that are associated with high mortality. However, data on the bactericidal and synergistic activity for clinically implemented antibiotics are scarce. Time-kill analyses were performed on two clinical isolates (AU1 and AU2) and the reference strain ATCC 700306 for penicillin (PG), ceftriaxone (CRO), gentamicin (GEN), daptomycin (DAP) and their combinations. AU1 and AU2 were CRO-resistant (MICs, 2 µg/mL) and ATCC 700306 was high-level GEN-resistant (MIC, 512 µg/mL), whereas all strains were PG- and DAP-susceptible (MICs, ≤0.125 and ≤1 µg/mL, respectively). CFU counts were determined at various time points from 0 to 48 h. All experiments were performed at 0.5×, 1×, 2× and 4× MIC. PG and CRO were not bactericidal for all strains, whereas DAP exhibited bactericidal activity at all concentrations for AU2 and ATCC 700306. The combination of PG or CRO with GEN was bactericidal for AU1 and AU2 at antibiotic concentrations ≥1× MIC. Bactericidal synergism was detected for PG or CRO combined with GEN in the two clinical isolates. PG plus CRO showed non-bactericidal synergism for ATCC 700306. DAP with GEN was synergistic at 1× MIC for AU1, whereas the killing activity of DAP was too pronounced to detect potential synergism in AU2. The combination of PG or CRO with GEN is synergistic and bactericidal. Moreover, these in vitro data suggest that DAP may represent a potential bactericidal treatment alternative against A. urinae. This finding could be important for the treatment of patients with a ß-lactam allergy or renal insufficiency.