In Vitro Effect of Multiple Antibiotic/Antimicrobial Residues on the Selection for Resistance in Bacteria

1992 ◽  
Vol 75 (4) ◽  
pp. 738-741 ◽  
Author(s):  
Marietta Sue Brady ◽  
Stanley E Katz

Abstract A method using a gram-positive and a gram-negative organism was used to investigate the selection for resistant populations after exposure to residue levels of 7 antibiotics and 1 antimicrobial. The organisms were exposed to individual compounds and combinations of 3 compounds for 14 days. The changes in minimum inhibitory concentration (MIC) of a panel of 8 antibiotics and 1 antimicrobial were used as the measure of resistance development/selection. For Staphylococcus aureus ATCC 9144, exposure to residue levels of oxytetracycline, tylosin, penicillin, and virginiamycin resulted in an increased MIC of the compound itself; most individual residues did not result in increased cross-resistance. With combinations of residues, 13 of 45 determinations resulted in significant increases in MIC. Enterobacter cloacae B520, which was much less sensitive to 4 of 9 markers, showed MIC increases only for tylosin and the combination of neomycin-sulfamethazine-oxytetracycline. The results indicate an interaction among residue levels of antibiotics in selection for resistance.

2001 ◽  
Vol 91 (8) ◽  
pp. 776-781 ◽  
Author(s):  
Wolfram Köller ◽  
W. F. Wilcox

In the United States, populations of the apple scab pathogen Venturia inaequalis have progressed through three consecutive rounds of fungicide resistance development, first to dodine, then to the benzimidazoles, and most recently to the sterol demethylation inhibitors (DMIs). Analysis of extensive monitoring data have to date provided no indication of detectable cross-resistance or partial cross-resistance of V. inaequalis populations to the three unrelated classes of fungicides prior to the selection of resistant subpopulations. However, in this study, resistance to both benomyl and DMIs developed to significantly higher frequencies within the previously established dodine-resistant population than in the population sensitive to dodine. Accelerated selection of phenotypes double resistant to dodine and the DMI fenarimol was apparent over the course of distinct seasons of apple scab management with either dodine or fenarimol. The data provide evidence for an accelerated speed of resistance development among phenotypes of V. inaequalis already resistant to an unrelated fungicide. This finding represents a departure from the previous model, which assumed entirely independent rounds of resistance developments. The data indicate that phenotypes of V. inaequalis might not only be selected for the trait of fungicide resistance but also for traits allowing a more flexible response to changes in the environment where they compete.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Alberta Ade ◽  
Cedric D. K. Amengor ◽  
Abena Brobbey ◽  
Isaac Ayensu ◽  
Benjamin K. Harley ◽  
...  

A library of six novel phenylhydrazones were synthesized and evaluated for their in vitro antimicrobial and resistance modulating activity against a panel of Gram-positive, Gram-negative, and fungal species. The compounds were produced in good yields of 60–92% w/w and characterized using melting point, UV-visible spectroscopy, infrared, and nuclear magnetic resonance (1H, 13C, and DEPT-Q) techniques. Mass spectroscopy was used to confirm the identity of one of the most active compounds, 5 [SA5]. The phenylhydrazones showed activity against all the six selected microorganisms with minimum inhibitory concentration (MIC) values of the most active compounds, 1 [BP1] and 5 [SA5], at 138 µM (Klebsiella pneumoniae) and 165 µM (Streptococcus pneumoniae), respectively. Compound 1 [BP1] further demonstrated a high resistance modulatory activity at 1.078 µM against Streptococcus pneumoniae and Klebsiella pneumoniae.


2020 ◽  
Vol 7 (4) ◽  
pp. 154
Author(s):  
Giovanni Cilia ◽  
Filippo Fratini ◽  
Elena della Buona ◽  
Fabrizio Bertelloni

Environmental resistance is an important factor for understanding the epidemiology of leptospirosis. Recently, new Leptospira hosts were identified, including also marine mammals. Moreover, halotolerant Leptospira strain, isolated from the environment and animals, highlighted the capability of this microorganism to persist in the seawater. The aim of this research was to investigate the bacteriostatic and bactericidal effect of salt on Leptospira strains belonging to 16 different serovars. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were verified through the microdilutions method starting from a 20% sodium chloride concentration. MIC values obtained were between 0.3125% and 10% of salt, while MBC values between 0.625% and >20%. Icterohaemorrhagiae (MIC: 0.3125%; MBC: 0.625%) resulted the most inhibited serovar, while the most resistant was Tarassovi (MIC: 10%; MBC: >20%). Interestingly, trends were reported for Pomona (MIC: 1.25%; MBC: >20%) and Bratislava (MIC: 0.625%; MBC: 20%), highlighting low MIC values but high MBC values. This is the first investigation aimed at the in vitro effect of salt on the growth of Leptospira spp. reference strains.


2019 ◽  
Vol 58 (3) ◽  
pp. 404-407 ◽  
Author(s):  
Fruzsina Nagy ◽  
Zoltán Tóth ◽  
Lajos Daróczi ◽  
Adrien Székely ◽  
Andrew M Borman ◽  
...  

Abstract Candida auris biofilms exhibit decreased susceptibility to echinocandins, which is associated with poorer clinical outcomes. Farnesol is a quorum-sensing molecule enhancing the activity of antifungals; therefore, we evaluated the in vitro effect of farnesol with anidulafungin, caspofungin, or micafungin against biofilms using fractional inhibitory concentration indexes (FICI), Bliss independence model, LIVE/DEAD-assay and scanning electron microscopy. Based on mathematical models, farnesol caused synergism in eleven out of twelve cases (FICIs range 0.133-0.507; Bliss synergy volume range 70.39–204.6 μM2%). This was confirmed by microscope images of combination-exposed biofilms. Our study showed the prominent effect of farnesol with echinocandins against C. auris biofilms.


2000 ◽  
Vol 14 (10) ◽  
pp. 891-894 ◽  
Author(s):  
Diane E Taylor

Resistance ofHelicobacter pylorito antibiotics ranges from 3% to 10% and may exceed these levels in some countries. The pathophysiology of clarithromycin resistance is reviewed, including the mode of action by which the antibiotic inhibits protein synthesis and the mechanism of resistance, which involves a mutation at position 2142 or 2143 in the V loop domain of the 23S rRNA genes. Mutations of A2142G confer a higher minimum inhibitory concentration than mutations of A2143G. The former demonstrate cross-resistance to macrolide, lincosamide and streptogramin antibiotics, whereas the latter are susceptible to streptogramin B. In vitro mutagenesis combined with natural transformation were used to create several types of clarithromycin-resistant mutants.H pyloristrains with A2142G and A2143G mutations had a higher growth rate than those with A2142C, A2143 or A2142T mutations. Data from this study indicate why clarithromycin-resistant clinical isolates ofH pyloriare more likely to have A2142G or A2143G mutations and only occasionally A2142C mutations.


Parasitology ◽  
1998 ◽  
Vol 117 (6) ◽  
pp. 541-545 ◽  
Author(s):  
B. PRADINES ◽  
M. MABIKA MAMFOUMBI ◽  
D. PARZY ◽  
M. OWONO MEDANG ◽  
C. LEBEAU ◽  
...  

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0·8 to 34·8 nm (mean IC50 5·0 nm) and the 95% confidence interval (CI95%) was 3·6–6·3 nm. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2=0·45, P<0·001), artemether and chloroquine (r2=0·36, P<0·001), artemether and quinine (r2=0·31, P<0·001), and artemether and halofantrine r2=0·19, P<0·01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.


2014 ◽  
Vol 59 (1) ◽  
pp. 467-474 ◽  
Author(s):  
Michael D. Huband ◽  
Patricia A. Bradford ◽  
Linda G. Otterson ◽  
Gregory S. Basarab ◽  
Amy C. Kutschke ◽  
...  

ABSTRACTAZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potentin vitroantibacterial activity against key Gram-positive (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae,Streptococcus pyogenes, andStreptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzaeandNeisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance inS. aureus, and if mutants were obtained, the mutations mapped togyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration andin vitrotime-kill studies. Inin vitrocheckerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potentin vitroantibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.


1988 ◽  
Vol 71 (2) ◽  
pp. 295-298
Author(s):  
Marietta Suebrady ◽  
Robert J Strobel ◽  
Stanley E Katz

Abstract An analytical procedure, based on the concept that exposure of bacteria to antibiotics will result in the selection of a resistant population, was developed. Two strains of enteric bacteria, Escherichia coli CS-1 and Enterobacter cloacae B520, which are sensitive to a wide variety of antibiotics, were used as the test organisms. E. coli CS-1 were exposed to 1.00 μg antibiotic or antimicrobial/mL; E. cloacae B520 were exposed to 0.01, 0.10, 0.50,1.00, and 5.00 μg/mL. Both organisms developed increased resistance to other antibiotics after exposure to chlortetracycline and oxytetracycline, as measured by the minimum inhibitory concentration (MIC). E. cloacae B520 showed increased resistance to ampicillin, oxytetracycline, and chloramphenicol after exposure to levels as low as 0.10 μg/mL. Exposure to streptomycin, sulfamethazine, tylosin, bacitracin, flavomycin, virginiamycin, and monensin at levels of 1.00 μg/mL did not increase the MIC. Exposure to 5.00 *tg streptomycin, sulfamethazine, tylosin, and monensin/mL increased the MIC ofE. cloacae to one of the antibiotic markers. These increased MICs exceeded the 95% confidence limits of the MIC values of the unexposed organisms.


1993 ◽  
Vol 56 (3) ◽  
pp. 229-233 ◽  
Author(s):  
MARIETTA SUE BRADY ◽  
NICHOLAS WHITE ◽  
STANLEY E. KATZ

Staphylococcus aureus ATCC 9144 was exposed to “safe levels” of ampicillin, dihydrostreptomycin, erythromycin, neomycin, oxytetracycline, and sulfamethazine, singly and in combinations of three drugs, for a 14-d interval, transferring daily. After the 14-d exposure interval, the minimum inhibitory concentration (MIC) of the organism for each treatment was determined for nine antibiotics/antimicrobials. There was one increase in the MIC out of 81 possibilities for the control or an incidence of 1.23%. There were four increases in the MIC in the single drug exposures for 54 possible increases in the MIC or an incidence of 7.40%. For the 18 combinations of three drugs, there were 55 increases in the MIC for 162 possible increases or 33.95%. This was an increase of 27.6 times over the control incidence and 4.6 times over the single drug incidence. The single drug incidence is 6.0 times the control incidence. These data indicate that the “safe levels” of antibiotics/antimicrobials that can appear in milk have the strong potential to select for antibiotic/antimicrobial-resistant bacterial populations.


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