scholarly journals In VitroActivities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK 771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in Humans, Including Isolates with Defined Resistance Mechanisms

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
G. Xue ◽  
D. M. Crabb ◽  
L. Xiao ◽  
Y. Liu ◽  
K. B. Waites
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Antimicrobial Agents ◽  
Mycoplasma Hominis ◽  
Mycoplasma Genitalium ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Content Type ◽  
Type Strains

ABSTRACTLevonadifloxacin (WCK 771) was evaluated against 68 type strains and clinical isolates ofMycoplasma genitalium,Mycoplasma hominis,Mycoplasma pneumoniae, andUreaplasmaspp. in comparison with moxifloxacin, levofloxacin, tetracycline, and azithromycin or clindamycin. Levonadifloxacin MICs were ≤0.5 μg/ml forM. genitalium. MIC90s were 1 μg/ml forM. hominis, 0.125 μg/ml forM. pneumoniae, and 2 μg/ml forUreaplasmaspp. Levonadifloxacin merits further study for treating infections caused by these organisms.

scholarly journals In Vitro Activities of Eravacycline and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Ken B. Waites ◽  
Donna M. Crabb ◽  
Li Xiao ◽  
Lynn B. Duffy ◽  
Sixto M. Leal
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Ureaplasma Urealyticum ◽  
Mycoplasma Hominis ◽  
Mycoplasma Genitalium ◽  
Content Type ◽  
Ureaplasma Parvum

ABSTRACT We performed in vitro susceptibility testing for eravacycline in comparison to 4 other antimicrobials against 10 Mycoplasma genitalium, 40 Mycoplasma hominis, 44 Mycoplasma pneumoniae, 20 Ureaplasma parvum, and 20 Ureaplasma urealyticum isolates. All eravacycline MICs were ≤0.25 μg/ml, except that for one isolate of M. genitalium, for which the MIC was 2 μg/ml. Eravacycline was markedly more potent than tetracycline, azithromycin, moxifloxacin, and clindamycin against all isolates tested, which included 37 macrolide, tetracycline, and/or fluoroquinolone-resistant organisms.

scholarly journals In Vitro Activities of Gepotidacin (GSK2140944) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Ken B. Waites ◽  
Donna M. Crabb ◽  
Li Xiao ◽  
Lynn B. Duffy
Keyword(s):  
Topoisomerase Ii ◽  
Antimicrobial Agents ◽  
Ureaplasma Urealyticum ◽  
Mycoplasma Hominis ◽  
Mycoplasma Genitalium ◽  
Content Type ◽  
Topoisomerase Ii Inhibitor ◽  
Ureaplasma Parvum ◽  
Type Strains

ABSTRACTGepotidacin, a novel first-in-class triazaacenaphthylene topoisomerase II inhibitor, was tested against 85 type strains and clinical isolates ofMycoplasma pneumoniae,Mycoplasma hominis,Mycoplasma genitalium,Ureaplasma parvum, andUreaplasma urealyticumin comparison to levofloxacin, moxifloxacin, azithromycin or clindamycin, and tetracycline. Gepotidacin MIC90s (μg/ml) were 0.125 (M. pneumoniae), 0.032 (M. genitalium), 2 (M. hominis), and 8 (Ureaplasmaspecies). Gepotidacin activity was not affected by resistance to fluoroquinolones, tetracyclines, or macrolides in the strains tested. Gepotidacin merits further study for treating infections caused by these organisms.

scholarly journals Comparative In Vitro Activities of the Investigational Fluoroquinolone DC-159a and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas

2008 ◽  
Vol 52 (10) ◽  
pp. 3776-3778 ◽  
Author(s):  
Ken B. Waites ◽  
Donna M. Crabb ◽  
Lynn B. Duffy
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Antimicrobial Agents ◽  
Mycoplasma Hominis ◽  
Mycoplasma Genitalium ◽  
The Other ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Mycoplasma Fermentans

ABSTRACT The in vitro susceptibilities of 151 unique clinical isolates of Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma genitalium, and Ureaplasma species to DC-159a, an investigational fluoroquinolone, in comparison with those to other agents were determined. Macrolides were the most active agents against M. pneumoniae and M. genitalium, whereas clindamycin was most active against M. hominis. DC-159a MICs were ≤0.5 μg/ml for all Mycoplasma species and ≤4 μg/ml for ureaplasmas. DC-159a was the most active fluoroquinolone tested against M. pneumoniae and M. fermentans, and it was second to moxifloxacin against the other species. It was bactericidal against 10 M. pneumoniae isolates and demonstrated killing of ≥99.9% of the inoculum at 24 h for 2 isolates. The excellent in vitro activity of DC-159a demonstrates its potential for use in the treatment of infections due to mycoplasmas and ureaplasmas.

In vitro activities of acetylmidecamycin and other antimicrobials against human macrolide-resistant Mycoplasma pneumoniae isolates

2020 ◽  
Vol 75 (6) ◽  
pp. 1513-1517 ◽  
Author(s):  
Na Wang ◽  
Yunheng Zhou ◽  
Hong Zhang ◽  
Yang Liu
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Antimicrobial Agents ◽  
Mycoplasma Hominis ◽  
Clinical Isolates ◽  
Mycoplasma Species ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Ureaplasma Spp

Abstract Objectives To assess the in vitro activities of acetylmidecamycin, a 16-membered macrolide, and 11 other antimicrobial agents against human mycoplasmas. Methods A total of 187 clinical isolates, Mycoplasma pneumoniae (n = 110), Mycoplasma hominis (n = 26) and Ureaplasma species (n = 51), were included in this study. The MICs of 12 antimicrobial agents, including acetylmidecamycin, thiamphenicol, chloramphenicol and some other macrolides, fluoroquinolones and tetracyclines, for these clinical isolates were determined by the broth microdilution method. Results For M. pneumoniae, the MIC90 values of the tested macrolides were: acetylmidecamycin (1 mg/L)<josamycin (4 mg/L)<midecamycin (8 mg/L)<azithromycin (16 mg/L)<erythromycin (>128 mg/L). Thiamphenicol and chloramphenicol had the same MIC90 (2 mg/L). For Ureaplasma species, the MIC90 values were: acetylmidecamycin (0.25 mg/L)<josamycin (0.5 mg/L)=midecamycin<azithromycin (1 mg/L)=erythromycin. Chloramphenicol had a lower MIC90 (2 mg/L) than that of thiamphenicol (4 mg/L). For M. hominis, the MIC90 values were: acetylmidecamycin (0.25 mg/L)<josamycin (0.5 mg/L)<midecamycin (2 mg/L)<azithromycin (>128 mg/L)=erythromycin. The MIC90 values of chloramphenicol and thiamphenicol were 2 and 4 mg/L, respectively. Conclusions The results indicated that acetylmidecamycin and thiamphenicol are active in vitro against the most common mycoplasma species infecting humans, including those resistant to macrolides and fluoroquinolones. Acetylmidecamycin and thiamphenicol might be a promising option for clinicians to treat infections caused by Mycoplasma and Ureaplasma spp., particularly macrolide-resistant M. pneumoniae in paediatrics and fluoroquinolone-resistant M. hominis in adults. Further investigation of their clinical roles in treating infections caused by these organisms is warranted.

scholarly journals In VitroAntibacterial Activity of AZD0914 against Human Mycoplasmas and Ureaplasmas

2015 ◽  
Vol 59 (6) ◽  
pp. 3627-3629 ◽  
Author(s):  
Ken B. Waites ◽  
Donna M. Crabb ◽  
Lynn B. Duffy ◽  
Michael D. Huband
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Mycoplasma Hominis ◽  
Mycoplasma Genitalium ◽  
Dna Gyrase ◽  
Content Type

ABSTRACTIn this study, susceptibilities were determined for AZD0914, a spiropyrimidinetrione DNA gyrase inhibitor, azithromycin, doxycycline, and levofloxacin againstMycoplasmaandUreaplasmaspecies. The activity of AZD0914 was comparable to that of levofloxacin and doxycycline againstMycoplasma genitaliumandMycoplasma pneumoniae. The AZD0914 MIC90againstMycoplasma hominiswas 8-fold greater than that for levofloxacin. The AZD0914 MIC90againstUreaplasmaspecies was 4-fold less than that for azithromycin and 8-fold less than that for levofloxacin and doxycycline.

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

scholarly journals Prevalence of Antimicrobial Resistance among Clinical Isolates of Bacteroides fragilis Group in Canada in 2010-2011: CANWARD Surveillance Study

2011 ◽  
Vol 56 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
James A. Karlowsky ◽  
Andrew J. Walkty ◽  
Heather J. Adam ◽  
Melanie R. Baxter ◽  
Daryl J. Hoban ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Bacteroides Fragilis ◽  
Clinical Isolates ◽  
Surveillance Study ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Amoxicillin Clavulanate ◽  
Bacteroides Fragilis Group ◽  
Bacteroides Ovatus

ABSTRACTClinical isolates of theBacteroides fragilisgroup (n= 387) were collected from patients attending nine Canadian hospitals in 2010-2011 and tested for susceptibility to 10 antimicrobial agents using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method.B. fragilis(59.9%),Bacteroides ovatus(16.3%), andBacteroides thetaiotaomicron(12.7%) accounted for ∼90% of isolates collected. Overall rates of percent susceptibility were as follows: 99.7%, metronidazole; 99.5%, piperacillin-tazobactam; 99.2%, imipenem; 97.7%, ertapenem; 92.0%, doripenem; 87.3%, amoxicillin-clavulanate; 80.9%, tigecycline; 65.9%, cefoxitin; 55.6%, moxifloxacin; and 52.2%, clindamycin. Percent susceptibility to cefoxitin, clindamycin, and moxifloxacin was lowest forB. thetaiotaomicron(n= 49, 24.5%),Parabacteroides distasonis/P. merdae(n= 11, 9.1%), andB. ovatus(n= 63, 31.8%), respectively. One isolate (B. thetaiotaomicron) was resistant to metronidazole, and two isolates (bothB. fragilis) were resistant to both piperacillin-tazobactam and imipenem. Since the last published surveillance study describing Canadian isolates ofB. fragilisgroup almost 20 years ago (A.-M. Bourgault et al., Antimicrob. Agents Chemother. 36:343–347, 1992), rates of resistance have increased for amoxicillin-clavulanate, from 0.8% (1992) to 6.2% (2010-2011), and for clindamycin, from 9% (1992) to 34.1% (2010-2011).

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals In VitroSpectrum of Pexiganan Activity When Tested against Pathogens from Diabetic Foot Infections and with Selected Resistance Mechanisms

2015 ◽  
Vol 59 (3) ◽  
pp. 1751-1754 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Katie M. Simpson ◽  
David J. Farrell ◽  
Helio S. Sader ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Surveillance Program ◽  
Content Type ◽  
Diabetic Foot Infections ◽  
Antimicrobial Surveillance ◽  
Mueller Hinton ◽  
The Family ◽  
Infection Types

ABSTRACTPexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50and MIC90against all organisms tested from DFI were 16 and 32 μg/ml, respectively.Escherichia coli,Klebsiella pneumoniae,Citrobacter koseri,Enterobacter cloacae,Acinetobacterspecies, andPseudomonas aeruginosaMIC values ranged from 8 to 16 μg/ml. Pexiganan MIC values amongStaphylococcus aureus(methicillin-resistantS. aureus[MRSA] and methicillin-susceptibleS. aureus[MSSA]), beta-hemolytic streptococci, andEnterococcus faeciumranged from 8 to 32 μg/ml. Pexiganan activity was not adversely affected for members of the familyEnterobacteriaceaeorP. aeruginosathat produced β-lactamases or resistance mechanisms to other commonly used antimicrobial agents. Decreased susceptibility to vancomycin did not affect pexiganan activity againstS. aureusorE. faecium.Enterococcus faecalisappears to be intrinsically less susceptible to pexiganan (MIC, 32 to 256 μg/ml). The “all organism” MIC90of 32 μg/ml for pexiganan in this study was >250-fold below the pexiganan concentration in the cream/delivery vehicle being developed for topical use.

scholarly journals In Vitro Activity of Eravacycline against Gram-Positive Bacteria Isolated in Clinical Laboratories Worldwide from 2013 to 2017

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Ian Morrissey ◽  
Stephen Hawser ◽  
Sibylle H. Lob ◽  
James A. Karlowsky ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Clinical Isolates ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Microdilution Method ◽  
Clinical Laboratories ◽  
Broth Microdilution Method ◽  
Doubling Dilution

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.

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