scholarly journals In VitroActivity of Biapenem plus RPX7009, a Carbapenem Combined with a Serine β-Lactamase Inhibitor, against Anaerobic Bacteria

2013 ◽  
Vol 57 (6) ◽  
pp. 2620-2630 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
Kerin L. Tyrrell ◽  
C. Vreni Merriam
Keyword(s):  
Anaerobic Bacteria ◽  
Fusobacterium Nucleatum ◽  
Fusobacterium Necrophorum ◽  
Beta Lactamase ◽  
Content Type ◽  
Agar Dilution ◽  
Fusobacterium Varium ◽  
Group Species ◽  
Gram Positive Cocci ◽  
Lactamase Inhibitor

ABSTRACTBiapenem is a carbapenem being developed in combination with RPX7009, a new inhibitor of serine β-lactamases. Biapenem was tested alone and in combination with fixed concentrations of RPX7009 by agar dilution against 377 recent isolates of anaerobes. A separate panel of 27 isolates ofBacteroidesspp. with decreased susceptibility or resistance to imipenem was also tested. Comparator drugs included meropenem, piperacillin-tazobactam, ampicillin-sulbactam, cefoxitin, ceftazidime, metronidazole, clindamycin, and tigecycline plus imipenem, doripenem, and ertapenem for the 27 selected strains. For recent consecutive strains ofBacteroidesspecies, the MIC90for biapenem-RPX7009 was 1 μg/ml, with a MIC90of 4 μg/ml for meropenem. OtherBacteroides fragilisgroup species showed a MIC90of 0.5 μg/ml for both agents. The MIC90s for biapenem-RPX7009 were 0.25 μg/ml forPrevotellaspp., 0.125 μg/ml forFusobacterium nucleatumandFusobacterium necrophorum, 2 μg/ml forFusobacterium mortiferum, 0.5 μg/ml forFusobacterium varium, ≤0.5 μg/ml for Gram-positive cocci and rods, and 0.03 to 8 μg/ml for clostridia. Against 5B. fragilisstrains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those of other carbapenems (≥32 μg/ml). AgainstBacteroidesstrains with an imipenem MIC of 2 μg/ml, biapenem-RPX7009 had MICs of 0.5 to 2 μg/ml, with MICs of 0.5 to 32 μg/ml for meropenem, doripenem, and ertapenem. For strains with an imipenem MIC of 4 μg/ml, the MICs for biapenem-RPX7009 were 4 to 16 μg/ml, with MICs of 8 to >32 μg/ml for meropenem, doripenem, and ertapenem. The inhibitor RPX7009 had no antimicrobial activity when tested alone, and it showed little or no potentiation of biapenem versus anaerobes. Biapenem-RPX7009 showed activity comparable to that of imipenem and was superior to meropenem, doripenem, and ertapenem against imipenem-nonsusceptibleBacteroidesspp.

scholarly journals Susceptibilities of bovine summer mastitis bacteria to antimicrobial agents.

1996 ◽  
Vol 40 (1) ◽  
pp. 157-160 ◽  
Author(s):  
H Jousimies-Somer ◽  
S Pyörälä ◽  
A Kanervo
Keyword(s):  
Antimicrobial Agents ◽  
Anaerobic Bacteria ◽  
Fusobacterium Necrophorum ◽  
Penicillin G ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Beta Lactamase ◽  
Bacterial Isolates ◽  
Amoxicillin Clavulanate ◽  
Agar Dilution

The susceptibility to 9 antimicrobial agents of 32 aerobic bacterial isolates and to 10 antimicrobial agents of 37 anaerobic bacterial isolates from 23 cases of bovine summer mastitis (16 Actinomyces pyogenes isolates, 8 Streptococcus dysgalactiae isolates, 3 S. uberis isolates, 3 S. acidominimus isolates, 2 Streptococcus spp., 15 Peptostreptococcus indolicus isolates, 10 Fusobacterium necrophorum isolates, and 12 isolates of anaerobic gram-negative rods) was determined by the agar dilution method. All isolates except one Bacteroides fragilis isolate (beta-lactamase producer) were susceptible to penicillin G, amoxicillin, amoxicillin-clavulanate, cefoxitin, clindamycin, and chloramphenicol (the B. fragilis strain was susceptible to the last four), which had MICs at which 90% of isolates were inhibited (MIC90s) of < or = 0.06, < or = 0.06, < or = 0.06 0.25, < or = 0.06, and 4.0 micrograms/ml, respectively. Spiramycin was active against the gram-positive aerobes (MIC90, 1.0 microgram/ml) but not against the anaerobes (MIC90, 16.0 micrograms/ml). Similar trends were noted for susceptibilities of aerobic and anaerobic bacteria to ofloxacin (MIC90s, 2.0 and 8 micrograms/ml, respectively). Occasional strains of aerobic streptococci were resistant to oxytetracycline, but all anaerobes were susceptible. Tinidazole was active against all anaerobes (MIC90, 2.0 micrograms/ml). beta-Lactamase was produced only by the B. fragilis isolate.

scholarly journals In vitro activities of trovafloxacin against 557 strains of anaerobic bacteria.

1996 ◽  
Vol 40 (9) ◽  
pp. 2232-2235 ◽  
Author(s):  
H M Wexler ◽  
E Molitoris ◽  
D Molitoris ◽  
S M Finegold
Keyword(s):  
Antimicrobial Activity ◽  
Clinical Laboratory ◽  
Anaerobic Bacteria ◽  
Bacteroides Fragilis ◽  
National Committee ◽  
Dilution Technique ◽  
Agar Dilution ◽  
Group Species ◽  
Clostridium Spp

The antimicrobial activity of trovafloxacin for 557 strains of anaerobic bacteria was determined by the National Committee for Clinical Laboratory Standards-approved Wadsworth agar dilution technique. The species tested included Bacteroides fragilis (n = 91), other members of the B. fragilis group (n = 130), Campylobacter gracilis (n = 15), other Bacteroides spp. (n = 16), Prevotella spp. (n = 49), Porphyromonas spp. (n = 15), Fusobacterium spp. (n = 62), Bilophila wadsworthia (n = 24), Sutterella wadsworthensis (n = 21), Clostridium spp. (n = 61), Peptostreptococcus spp. (n = 38), and gram-positive non-spore-forming rods (n = 35). Trovafloxacin inhibited all strains of B. fragilis at < or = 0.5 microgram/ml, 99% of other B. fragilis group species at < or = 2 micrograms/ml, and 96% of all anaerobes tested at < or = 2 micrograms/ml.

scholarly journals In VitroActivity of Ceftazidime-NXL104 against 396 Strains of β-Lactamase-Producing Anaerobes

2011 ◽  
Vol 55 (7) ◽  
pp. 3616-3620 ◽  
Author(s):  
Diane M. Citron ◽  
Kerin L. Tyrrell ◽  
Vreni Merriam ◽  
Ellie J. C. Goldstein
Keyword(s):  
Anaerobic Bacteria ◽  
Bacteroides Fragilis ◽  
Mixed Infections ◽  
Constant Concentration ◽  
Content Type ◽  
Lactamase Inhibitor

ABSTRACTNXL104, a novel β-lactamase inhibitor, was tested at a constant concentration of 4 μg/ml in combination with ceftazidime (CAZ), with and without added metronidazole, against 396 β-lactamase-producing strains of anaerobic bacteria. MIC50/MIC90values forBacteroides fragilisand theB. fragilisgroup were 8/16 and 64/>128 μg/ml, respectively. Although CAZ-NXL104 had limited activity against most anaerobic strains, in combination with metronidazole it shows potential for treating mixed infections involving resistantEnterobacteriaceaeand anaerobes.

scholarly journals In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith
Keyword(s):  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Clinical Issue ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

scholarly journals Pharmacodynamics of Imipenem in Combination with β-Lactamase Inhibitor MK7655 in a Murine Thigh Model

2014 ◽  
Vol 59 (2) ◽  
pp. 790-795 ◽  
Author(s):  
Eleftheria Mavridou ◽  
Ria J. B. Melchers ◽  
Anita C. H. A. M. van Mil ◽  
E. Mangin ◽  
Mary R. Motyl ◽  
...  
Keyword(s):  
Dose Fractionation ◽  
Maximum Effect ◽  
Significant Activity ◽  
Beta Lactamase ◽  
Time Curve ◽  
Unbound Fraction ◽  
Content Type ◽  
Concentration Time ◽  
Lactamase Inhibitor

ABSTRACTMK7655 is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. Pharmacokinetics (PK) of imipenem-cilastatin (IMP/C) and MK7655 were determined for intraperitoneal doses of 4 mg/kg to 128 mg/kg of body weight. MIC and pharmacodynamics (PD) studies of MK7655 were performed against several beta-lactamase producingPseudomonas aeruginosaandKlebsiella pneumoniaestrains to determine its effectin vitroandin vivo. Neutropenic mice were infected in each thigh 2 h before treatment with an inoculum of approximately 5 × 106CFU. They were treated with IMP/C alone (every 2 hours [q2h], various doses) or in combination with MK7655 in either a dose fractionation study or q2h for 24 h and sacrificed for CFU determinations. IMP/MK7655 decreased MICs regarding IMP MIC. The PK profiles of IMP/C and MK7655 were linear over the dosing range studied and comparable with volumes of distribution (V) of 0.434 and 0.544 liter/kg and half-lives (t1/2) of 0.24 and 0.25 h, respectively. Protein binding of MK7655 was 20%. A sigmoidal maximum effect (Emax) model was fit to the PK/PD index responses. The effect of the inhibitor was not related to the maximum concentration of drug in serum (Cmax)/MIC, and model fits forT>MICand area under the concentration-time curve (AUC)/MIC were comparable (R2of 0.7 and 0.75), but there appeared to be no significant relationship of effect with dose frequency. Escalating doses of MK7655 and IMP/C showed that the AUC of MK7655 required for a static effect was dependent on the dose of IMP/C and the MIC of the strain, with a mean area under the concentration-time curve for the free, unbound fraction of the drug (fAUC) of 26.0 mg · h/liter. MK7655 shows significant activityin vivoand results in efficacy of IMP/C in otherwise resistant strains. The exposure-response relationships found can serve as a basis for establishing dosing regimens in humans.

scholarly journals In Vitro Activities of a New Des-Fluoro(6) Quinolone, Garenoxacin, against Clinical Anaerobic Bacteria

2003 ◽  
Vol 47 (11) ◽  
pp. 3667-3671 ◽  
Author(s):  
A. Liebetrau ◽  
A. C. Rodloff ◽  
J. Behra-Miellet ◽  
L. Dubreuil
Keyword(s):  
Clostridium Difficile ◽  
Anaerobic Bacteria ◽  
Bacteroides Fragilis ◽  
Antimicrobial Activities ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Positive ◽  
Agar Dilution ◽  
Gram Positive Cocci

ABSTRACT The antimicrobial activities of garenoxacin and eight other antibiotics against 641 anaerobic isolates were evaluated with the NCCLS agar dilution method. Overall, the MICs of garenoxacin for 50 and 90% of the strains tested (in micrograms per milliliter) were as follows: Bacteroides fragilis group, 0.5 and 2; Prevotella spp., 0.25 and 2; Fusobacterium spp., 0.25 and 0.5; Porphyromonas spp., 0.125 and 0.25; Bilophila wadsworthia, 0.5 and 1; Veillonella spp., 0.25 and 0.5; Clostridium spp., 0.25 and 1; Clostridium difficile, 2 and >64; Bifidobacterium spp., 1 and 2; Eggerthella lenta, 0.25 and 1; Propionibacterium spp., 0.5 and 0.5; gram-positive cocci, 0.125 and 0.25.

scholarly journals Reconciling the Potentially Irreconcilable? Genotypic and Phenotypic Amoxicillin-Clavulanate Resistance in Escherichia coli

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Timothy J. Davies ◽  
Nicole Stoesser ◽  
Anna E. Sheppard ◽  
Manal Abuoun ◽  
Philip Fowler ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Fixed Effects ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Content Type ◽  
Genetic Features ◽  
Amoxicillin Clavulanate ◽  
Doubling Dilution ◽  
Agar Dilution ◽  
Phenotypic Methods

ABSTRACT Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, and yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 Escherichia coli bloodstream infection isolates from Oxfordshire, United Kingdom, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). A total of 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity, 23% [78/339]) but improved when genetic features associated with penicillinase hyperproduction (e.g., promoter mutations and copy number estimates) were considered (sensitivity, 82% [277/339]; P < 0.0001). Most discrepancies occurred in isolates with MICs within ±1 doubling dilution of the breakpoint. We investigated two potential causes: the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement (±1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.

scholarly journals Multicenter Clinical Evaluation of Etest Meropenem-Vaborbactam (bioMérieux) for Susceptibility Testing of Enterobacterales (Enterobacteriaceae) and Pseudomonas aeruginosa

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Sophonie Jean ◽  
Sheri Garrett ◽  
Claire Anglade ◽  
Laurence Bridon ◽  
Leanne Davies ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Reference Method ◽  
Individual Species ◽  
Beta Lactamase ◽  
Content Type ◽  
European Committee ◽  
Tract Infections ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACT Meropenem-vaborbactam (MEV) is a novel carbapenem–beta-lactamase inhibitor combination antibiotic approved by the U.S. Food and Drug Administration (FDA) for treatment of complicated urinary tract infections, including pyelonephritis, in adults. In this study, we evaluated the performance of Etest MEV (bioMérieux, Marcy l’Etoile, France) compared to that of broth microdilution for 629 Enterobacterales and 163 Pseudomonas aeruginosa isolates. According to CLSI/FDA breakpoints, 13 Enterobacterales isolates (12 clinical and 1 challenge) were resistant to MEV. Overall, Etest MEV demonstrated 92.4% essential agreement (EA), 99.2% category agreement (CA), 0% very major errors (VME), 0% major errors (ME), and 0.8% minor errors (mE) with clinical and challenge isolates of Enterobacterales. Individual species demonstrated EA rates of ≥80%, with the exception of Proteus mirabilis, for which clinical and challenge isolates demonstrated 34.3% EA, 97.1% CA, 0% ME, and 2.9% mE, precluding the use of Etest MEV with this species. Excluding P. mirabilis, MEV Etest MEV demonstrated 95.8% EA, 99.3% CA, 0% VME, 0% ME, and 0.7% mE with Enterobacterales isolates. When evaluated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, Etest MEV performance with clinical (16 MEV resistant) and challenge (12 MEV resistant) isolates of Enterobacterales (excluding P. mirabilis) and P. aeruginosa demonstrated an unacceptably high VME rate of 7.1% despite 95.2% EA, 99.2% CA, and 0.5% ME compared to the reference method. In conclusion, we report that Etest MEV is accurate and reproducible for MEV susceptibility testing for P. aeruginosa and Enterobacterales, with the exception of P. mirabilis, using CLSI/FDA breakpoints. Etest MEV should not be used with P. mirabilis due to unacceptable analytical performance.

Anaerobic bacteria

2020 ◽  
pp. 1055-1060
Author(s):  
Anilrudh A. Venugopal ◽  
David W. Hecht
Keyword(s):  
Supportive Care ◽  
Anaerobic Bacteria ◽  
Anaerobic Infection ◽  
Gram Negative ◽  
Commensal Flora ◽  
Gram Staining ◽  
Affected Tissue ◽  
Different Levels ◽  
Gram Positive Cocci ◽  
Lactamase Inhibitor

Anaerobic bacteria will not grow when incubated with 10% CO2 in room air, but they vary in their tolerance of different levels of oxygen. Anaerobic bacteria are important commensal flora of the skin and oral, intestinal, and pelvic mucosae, and are classified according to their Gram-staining characteristics and ability to produce spores: (1) Gram-positive—cocci, non-spore-forming bacilli, and spore-forming bacilli (notably the Clostridium spp.); (2) Gram-negative—cocci and bacilli. Many anaerobic bacteria possess virulence factors that facilitate their pathogenicity (e.g. histolytic enzymes and various toxins). A putrid odour of the affected tissue or drainage is highly suggestive of an anaerobic infection, as is the presence of gas in tissues. Aside from supportive care, treatment requires drainage of abscesses and resection of devitalized tissue; and antibiotics—agents that are active against anaerobes include clindamycin, metronidazole, vancomycin, β‎-lactam/β‎-lactamase inhibitor combinations, carbapenems, moxifloxacin, tigecycline, chloramphenicol, and even macrolides.

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