scholarly journals In Vitro and In Vivo Evaluations of β-Lactam/β-Lactamase Mono- and Combined Therapies against Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan

2020 ◽  
Vol 8 (12) ◽  
pp. 1981
Author(s):  
Tsung-Ying Yang ◽  
Ya-Ju Hsieh ◽  
Li-Ting Kao ◽  
Guan-Hong Liu ◽  
Shao-Hsuan Lian ◽  
...  

Increasing carbapenem resistance rates worldwide underscored the urgent need of novel antimicrobials. Ceftazidime–avibactam and aztreonam–avibactam combinations are developed to combat carbapenem resistance, but biological and geographic variations must be considered for antibiotic susceptibility patterns varied. Thus, we sought to assess the susceptibilities of ceftazidime–avibactam and aztreonam–avibactam against 660 carbapenem-nonsusceptible Enterobacteriaceae isolates (472 Klebsiella pneumoniae and 188 Escherichia coli) collected during an earlier Taiwan surveillance study. Agar dilution method was used to determine ceftazidime–avibactam and aztreonam–avibactam susceptibility. Metallo-carbapenemase’s contribution to resistance were investigated with EDTA addition. The in vivo efficacies were evaluated using a Caenorhabditis elegans model. High susceptibility rates were observed for ceftazidime–avibactam and aztreonam–avibactam against the 472 carbapenem-nonsusceptible K. pneumoniae (CnsKP) (85.2% and 95.3%, respectively) and 188 carbapenem-nonsusceptible E. coli (CnsEC) isolates (91.5% and 94.1%, respectively). For non-metallo-carbapenemase producers, the susceptibility rates for ceftazidime–avibactam were 93.6% for CnsKP and 97.7% for CnsEC, whereas only 7.1% CnsKP and 11.1% CnsEC in metallo-carbapenemase producers were susceptible to ceftazidime–avibactam. Of all isolates, 95.3% CnsKP and 94.1% CnsEC were susceptible to aztreonam–avibactam. In C. elegans model, ceftazidime–avibactam and aztreonam–avibactam revealed effective against a blaKPC-producing K. pneumoniae isolate in vivo. Our results propose a positive therapeutic approach for both combinations against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

2013 ◽  
Vol 59 (4) ◽  
pp. 252-259 ◽  
Author(s):  
Lei Han ◽  
Jin'e Lei ◽  
Shaoshan Han ◽  
Li He ◽  
Chaofeng Ma ◽  
...  

Listeria monocytogenes is resistant to fosfomycin in vitro but is susceptible in vivo due to increased expression of positive regulator factor A (PrfA) and its dependent factor, hexose phosphate transporter (Hpt), upon infection of host cells. Amberlite, a polymeric adsorbent resin, could induce PrfA-dependent gene expression and thus, in theory, improve the sensitivity of L. monocytogenes to fosfomycin in vitro. In the current study, an improved susceptibility test based on Amberlite was developed using reference strains. Thirty-five clinical isolates were further examined to verify those preliminary results. Briefly, Amberlite increased in vitro fosfomycin sensitivity of all strains. Optimal Amberlite concentrations, as evaluated through the expression of phospholipase B (PlcB) and Hpt, were 10% and 15% (w/v) in agar media and 3% (w/v) in broth media. Mueller–Hinton (MH) medium, tryptone soya (TS) medium, and brain heart infusion (BHI) medium were used to verify the results in the control strains using agar dilution and broth micro- and macro-dilution methods. Better listerial growth was shown in TS and BHI than in MH. Both broth dilution methods yielded lower minimal inhibitory concentration (MIC) of fosfomycin than the agar dilution method. The MIC of fosfomycin for 35 clinical isolates was 2–32 μg/mL, suggesting improved susceptibility. In conclusion, in vitro sensitivity of L. monocytogenes to fosfomycin was substantially improved in the presence of 3% Amberlite-supplemented TSB or BHIB and the broth microdilution method. This improved method revealed the potential antilisterial activity of fosfomycin in vitro and could facilitate the therapy of listeriosis using fosfomycin.


2000 ◽  
Vol 44 (11) ◽  
pp. 3133-3136 ◽  
Author(s):  
Alexandra Aubry ◽  
Vincent Jarlier ◽  
Sylvie Escolano ◽  
Chantal Truffot-Pernot ◽  
Emmanuelle Cambau

ABSTRACT In vitro activities of 17 antibiotics against 53 clinical strains of Mycobacterium marinum, an atypical mycobacterium responsible for cutaneous infections, were determined using the reference agar dilution method. Rifampin and rifabutin were the most active drugs (MICs at which 90% of the isolates tested were inhibited [MIC90s], 0.5 and 0.6 μg/ml, respectively). MICs of minocycline (MIC90, 4 μg/ml), doxycycline (MIC90, 16 μg/ml), clarithromycin (MIC90, 4 μg/ml), sparfloxacin (MIC90, 2 μg/ml), moxifloxacin (MIC90, 1 μg/ml), imipenem (MIC90, 8 μg/ml), sulfamethoxazole (MIC90, 8 μg/ml) and amikacin (MIC90, 4 μg/ml) were close to the susceptibility breakpoints. MICs of isoniazid, ethambutol, trimethoprim, azithromycin, ciprofloxacin, ofloxacin, and levofloxacin were above the concentrations usually obtained in vivo. For each drug, the MIC50, geometric mean MIC, and modal MIC were very close, showing that all the strains had a similar susceptibility pattern. Percent agreement (within ±1 log2 dilution) between MICs yielded by the Etest method and by the agar dilution method used as reference were 83, 59, 43, and 24% for minocycline, rifampin, clarithromycin, and sparfloxacin, respectively. Reproducibility with the Etest was low, in contrast to that with the agar dilution method. In conclusion, M. marinum is a naturally multidrug-resistant species for which the agar dilution method is more accurate than the Etest for antibiotic susceptibility testing.


2015 ◽  
Vol 59 (9) ◽  
pp. 5220-5225 ◽  
Author(s):  
Magnus Unemo ◽  
Johan Ringlander ◽  
Catherine Wiggins ◽  
Hans Fredlund ◽  
Susanne Jacobsson ◽  
...  

ABSTRACTResistance inNeisseria gonorrhoeaeagainst all antimicrobials available for the treatment of gonorrhea has emerged. The first gonococcal strains with high-level resistance to ceftriaxone, the last option for first-line empirical antimicrobial monotherapy, were recently described. Consequently, new treatment options are essential. In this study, thein vitroactivity of the novel spiropyrimidinetrione ETX0914 (AZD0914), a DNA topoisomerase II inhibitor, was investigated among contemporary consecutive clinicalN. gonorrhoeaeisolates obtained in 21 European countries and compared to the activities of antimicrobials currently or previously recommended for treatment. Consecutive clinicalN. gonorrhoeaeisolates (n= 873) cultured in 21 European countries from 2012 to 2014 were examined for their susceptibility to ETX0914. The MICs of ETX0914 were determined using the agar dilution method. For comparison, the MICs of ceftriaxone, cefixime, azithromycin, and ciprofloxacin were determined using Etest or the agar dilution method. For ETX0914, the MIC range, modal MIC, MIC50, and MIC90were ≤0.002 to 0.25 mg/liter, 0.125 mg/liter, 0.064 mg/liter, and 0.125 mg/liter, respectively. The MIC values were substantially lower than those of the fluoroquinolone ciprofloxacin and most other antimicrobials examined. No cross-resistance with any other examined antimicrobial was observed. In conclusion, thein vitrosusceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical isolates from 21 European countries was high, and no cross-resistance to antimicrobials currently or previously used for gonorrhea treatment was indicated. Additional studies investigating thein vitroandin vivoinduction and mechanisms of ETX0914 resistance in gonococci, pharmacokinetics/pharmacodynamics in modeling/simulations and in humans, and performance in randomized controlled gonorrhea treatment trials are essential.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Séverine Boisard ◽  
Anne-Marie Le Ray ◽  
Anne Landreau ◽  
Marie Kempf ◽  
Viviane Cassisa ◽  
...  

During this study, thein vitroantifungal and antibacterial activities of different extracts (aqueous and organic) obtained from a French propolis batch were evaluated. Antifungal activity was evaluated by broth microdilution on three pathogenic strains:Candida albicans, C. glabrata, andAspergillus fumigatus. Antibacterial activity was assayed using agar dilution method on 36 Gram-negative and Gram-positive strains includingStaphylococcus aureus. Organic extracts showed a significant antifungal activity againstC. albicansandC. glabrata(MIC80between 16 and 31 µg/mL) but only a weak activity towardsA. fumigatus(MIC80= 250 µg/mL). DCM based extracts exhibited a selective Gram-positive antibacterial activity, especially againstS. aureus(SA) and several of its methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains (MIC10030–97 µg/mL). A new and active derivative of catechin was also identified whereas a synergistic antimicrobial effect was noticed during this study.


2008 ◽  
Vol 3 (9) ◽  
pp. 1934578X0800300 ◽  
Author(s):  
Mehrdad Iranshahi ◽  
Abdolmajid Fata ◽  
Bahareh Emami ◽  
Bibi Mohadeseh Jalalzadeh Shahri ◽  
Bibi Sedigheh Fazly Bazzaz

The increase in dermatophytoses and the fact that some patients do not respond well to therapy make it necessary to find new antifungal agents. As part of our ongoing studies on medicinal plants from Iran, we studied antidermatophytic activities of Ferula latisecta essential oil, which had shown considerable antifungal activity in preliminary antimicrobial screening. Antifungal activity was evaluated by determination of MIC values using the agar dilution method on type strains of Candida albicans and dermatophytes. The composition of the oil was characterized by GC and GC/MS analyses. The essential oil was rich in polysulfides (75.2%) and exhibited good activity against Trichophyton rubrum and T. verrucosom for about three weeks, with a MIC value 96 μg/mL. The oil showed antifungal activity, especially against dermatophytes, and the activity is probably related to the sulfur-containing components of the oil. This study has identified that the polysulfides-rich essential oil of Ferula latisecta fruits has activity against a range of human pathogenic dermatophytes, justifying future clinical trials to validate its use as a therapeutic alternative for dermatophytosis.


2002 ◽  
Vol 46 (9) ◽  
pp. 3068-3070 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
C. Vreni Merriam ◽  
Yumi A. Warren ◽  
Kerin L. Tyrrell ◽  
...  

ABSTRACT The in vitro susceptibilities of 170 clinical isolates plus 12 American Type Culture Collection strains of Pasteurella species comprising nine species and three Pasteurella multocida subspecies were studied by an agar dilution method. Garenoxacin (BMS-284756), a new des-fluoro(6) quinolone, was active at ≤0.06 μg/ml against all isolates, including four β-lactamase-producing strains, with >90% of the strains susceptible to ≤0.008 μg/ml. Garenoxacin was generally 1 to 2 dilutions more active than levofloxacin and moxifloxacin and was the most active agent tested. Cefoxitin required 1 μg/ml for inhibition of 51 of 182 (29%) of strains, and 3 strains (also β-lactamase producers) were resistant to doxycycline.


1996 ◽  
Vol 40 (6) ◽  
pp. 1419-1421 ◽  
Author(s):  
S J Martin ◽  
S L Pendland ◽  
C Chen ◽  
P Schreckenberger ◽  
L H Danziger

Combination antimicrobial therapy against Legionella species has not been well studied. Several quinolones have activity against Legionella strains, which prompted this in vitro search for a synergistic combination with the macrolides. By a checkerboard assay, erythromycin, clarithromycin, and azithromycin, each in combination with ciprofloxacin and levofloxacin, were tested for synergy against 46 isolates of Legionella. The agar dilution method was employed using buffered charcoal-yeast extract media. A final inoculum of 10(4) CFU per spot was prepared from 24-h growth of each isolate. Plates were incubated at 35 degrees C for 48 h. Synergy, partial synergy, additive effect, or indifference was observed for all combinations of antibiotics tested. There was no antagonism observed. Synergy occurred to a significantly greater extent for the clarithromycin-levofloxacin (P = 0.0001) and azithromycin-levofloxacin (P = 0.003) combinations versus erythromycin-levofloxacin. The azithromycin-ciprofloxacin combination demonstrated significantly greater synergy than did either erythromycin-ciprofloxacin (P = 0.003) or clarithromycin-ciprofloxacin (P = 0.001). The newer macrolides clarithromycin and azithromycin may be more active in combination with a fluoroquinolone than is erythromycin.


2003 ◽  
Vol 47 (7) ◽  
pp. 2145-2151 ◽  
Author(s):  
Po-Ren Hsueh ◽  
Lee-Jene Teng ◽  
Tsu-Lan Wu ◽  
Dine Yang ◽  
Wen-Kuei Huang ◽  
...  

ABSTRACT There is a high prevalence of β-lactam- and macrolide-resistant Streptococcus pneumoniae in Taiwan. To understand the in vitro susceptibilities of recent isolates of S. pneumoniae to fluoroquinolones and telithromycin (which is not available in Taiwan), the MICs of 23 antimicrobial agents for 936 clinical isolates of S. pneumoniae isolated from different parts of Taiwan from 2000 to 2001 were determined by the agar dilution method. Overall, 72% of isolates were not susceptible to penicillin (with 61% being intermediate and 11% being resistant) and 92% were resistant to erythromycin. Telithromycin MICs were ≥1 μg/ml for 16% of the isolates, and for 99% of these isolates the MICs of all macrolides tested were ≥256 μg/ml; all of these isolates had the constitutive macrolide-lincosamide-streptogramin B phenotype. Eighty-eight percent of the isolates were resistant to three or more classes of drugs. The ciprofloxacin MICs were ≥4 μg/ml for six (0.6%) isolates from five patients collected in 2000 and 2001, and the levofloxacin MICs were ≥8 μg/ml for five of these isolates. Seven isolates for which ciprofloxacin MICs were ≥4 μg/ml, including one isolate recovered in 1999, belonged to three serotypes (serotype 19F, five isolates; serotype 23A, one isolate; and serotype 23B, one isolate). The isolates from the six patients for which ciprofloxacin MICs were ≥4 μg/ml had different pulsed-field gel electrophoresis profiles and random amplified polymorphic DNA patterns, indicating that no clonal dissemination occurred over this time period. Despite the increased rate of fluoroquinolone use, the proportion of pneumococcal isolates for which ciprofloxacin MICs were elevated (≥4 μg/ml) remained low. However, the occurrence of telithromycin resistance is impressive and raises concerns for the future.


2002 ◽  
Vol 46 (12) ◽  
pp. 3995-3996 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
C. Vreni Merriam ◽  
Yumi A. Warren ◽  
Kerin L. Tyrrell ◽  
...  

ABSTRACT Garenoxacin (BMS 284756) was active against 105 of 108 (97%) recent clinical Gardnerella vaginalis isolates at ≤2 μg/ml by using the reference agar dilution method for anaerobes. Twenty-eight percent of isolates (31 of 108) were resistant to metronidazole, and 44% were resistant to doxycycline. All were susceptible to clindamycin and ampicillin-sulbactam.


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