Abstract:
:Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We describe the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered Escherichia coli isolates harboring mutant blaKPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam MICs were 1 and 0.03 µg/ml, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MICs ≤ 4 µg/ml). Against Klebsiella pneumoniae isolates harboring mutant blaKPC, the addition of vaborbactam lowered the meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates with mutant ompK36 porin genes (n = 26) than against those with wild-type ompK36 porin genes (n = 54) (0.25 versus 0.03 µg/ml; P < 0.0001). Against E. coli TOP10 isolates with plasmid constructs containing wild-type blaKPC or mutant blaKPC, the addition of vaborbactam at 8 µg/ml lowered the meropenem MICs 2- to 512-fold, resulting in meropenem-vaborbactam MICs of 0.03 µg/ml. The rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged from 90 to 95%. Essential agreement rates were higher for research-use-only (RUO) gradient strips manufactured by bioMérieux (82%) than for those manufactured by Liofilchem (48%) (P < 0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae isolates with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36 The results of susceptibility testing with RUO bioMérieux gradient strips most closely aligned with those of broth microdilution methods.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Wilson WR,Kline EG,Jones CE,Morder KT,Mettus RT,Doi Y,Nguyen MH,Clancy CJ,Shields RKdoi
10.1128/AAC.02048-18subject
Has Abstractpub_date
2019-02-26 00:00:00issue
3eissn
0066-4804issn
1098-6596pii
AAC.02048-18journal_volume
63pub_type
杂志文章abstract::An Escherichia coli strain with a plasmidic amikacin resistance has been selected for which the evidence strongly indicates that resistance is mediated by aminoglycoside phosphotransferase [APH(3')-II]: (i) this resistance was coupled with resistance against kanamycin and neomycin; (ii) partially purified APH(3')-II[A...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.344
更新日期:1981-09-01 00:00:00
abstract::Amoxicillin when administered with gastric acid suppressors has been shown to be effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim of this investigator-blind crossover study was to determine if gastric mucosal amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.39.9.2084
更新日期:1995-09-01 00:00:00
abstract::The emergence of clinical enterococcal isolates resistant to both ampicillin and vancomycin is a cause of great concern, as there are few therapeutic alternatives for treatment of infections caused by such organisms. We evaluated the effects of the combination of ampicillin with vancomycin against vancomycin-resistant...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.10.2201
更新日期:1992-10-01 00:00:00
abstract::The density of the biofilm layer produced on a plastic surface by 23 clinical isolates and 1 reference strain of slime-positive, coagulase-negative staphylococci was measured following growth in subinhibitory concentrations (sub-MICs) of cefamandole or vancomycin ranging from 2 to 0.008 micrograms/ml. All strains were...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.3.390
更新日期:1990-03-01 00:00:00
abstract::Various parameters were examined for their effects on interferon production with human fibroblast cells (FS-4) grown on microcarriers, using a superinduction procedure. Optimal concentrations of cycloheximide and actinomycin D during induction were 10 micrograms/ml, respectively. Cells required 5 to 6 h of exposure to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.1.130
更新日期:1980-07-01 00:00:00
abstract::An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, Z...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02024-17
更新日期:2018-04-26 00:00:00
abstract::The racemic nucleoside analogue 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC) is in clinical development for the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. dOTC is structurally related to lamivudine (3TC), but the oxygen and sulfur in the furanosyl ring are transposed. Intracellular metabolism ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.8.1835
更新日期:1999-08-01 00:00:00
abstract::The in vitro activities of four fluoroquinolone compounds were tested against 92 Escherichia coli strains of ovine and caprine origin under aerobic and anaerobic incubation conditions. The four fluoroquinolones proved to be highly effective against the E. coli isolates tested. When bacteria were cultured anaerobically...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.10.2469
更新日期:1994-10-01 00:00:00
abstract::Cefodizime, an iminomethoxy aminothiazolyl cephalosporin similar to moxalactam and ceftazidime, was less active (minimal inhibitory concentration, 1.6 to 12 micrograms) than cefazolin or cefotaxime against Staphylococcus aureus and Staphylococcus epidermidis. It inhibited Haemophilus and Neisseria spp. at less than 0....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.6.907
更新日期:1983-06-01 00:00:00
abstract::Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored do...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02214-15
更新日期:2016-03-25 00:00:00
abstract::The 747-bp cfiA gene, which encodes a metallo-beta-lactamase, and the regions flanking cfiA in six imipenem-resistant and four imipenem-susceptible Bacteroides fragilis strains isolated in Japan were analyzed by PCR and DNA sequencing. The nucleotide sequences of the cfiA genes (designated cfiA(1) to cfiA(10)) of all ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.3.979-985.2003
更新日期:2003-03-01 00:00:00
abstract::At least four broad-spectrum efflux pumps (Mex) are involved in elevated intrinsic antibiotic resistance as well as in acquired multidrug resistance in Pseudomonas aeruginosa. Substrate specificity of the Mex pumps has been shown to be determined by the cytoplasmic membrane component (MexB, MexD, MexF, and MexY) of th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.7.2169-2173.2002
更新日期:2002-07-01 00:00:00
abstract::The pharmacokinetic properties of an everninomicin antibiotic (SCH27899; Ziracin) were studied with healthy Japanese male volunteers by single (1, 3, 6, and 9 mg/kg of body weight) and multiple 60-min intravenous infusions (3, 6, and 9 mg/kg once daily for 10 consecutive days following a 2-day interval after the initi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.45.3.917-921.2001
更新日期:2001-03-01 00:00:00
abstract::A clinical isolate of Pseudomonas aeruginosa, PAe191, was found to be highly resistant to all anti-Pseudomonas beta-lactam antibiotics (except imipenem) and resistant also to aminoglycosides. It produced a beta-lactamase (with an apparent pI of 7.6) which was not inhibited by clavulanic acid. Cloning and characterizat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3113
更新日期:1998-12-01 00:00:00
abstract::Doxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME), a well-characterized disease and valuable model for tick-borne zoonoses. Conflicting reports of clearance of Ehrlichia canis after treatment with doxycycline suggested that the disease phase during which treatment is initiated influences o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01622-09
更新日期:2010-12-01 00:00:00
abstract::Using a real-time PCR assay specific for a mosaic penA allele that has been associated with oral cephalosporin resistance in Asia, 54 available Neisseria gonorrhoeae isolates collected in San Francisco, CA, from January to October 2008 were analyzed. Five isolates tested positive for the mosaic penA gene by real-time ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00406-09
更新日期:2009-09-01 00:00:00
abstract::Cefmenoxime, an investigational semisynthetic cephalosporin, was evaluated in 18 pediatric patients with a variety of infections. There were seven patients with urinary tract infections, two with wound infections, two with osteomyelitis, two with abscess infections, one with cervical adenitis, one with hidradenitis, o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.4.508
更新日期:1985-10-01 00:00:00
abstract::Exposure of Staphylococcus aureus to cloxacillin at neutral pH rendered the bacteria more susceptible to subsequent lysis by lysostaphin. This sensitization effect also occurred at lower pH levels which were nonpermissive for the bactericidal action of cloxacillin, but the effect disappeared at pH 5.0. These findings ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.4.618
更新日期:1982-04-01 00:00:00
abstract::A new 3-N-aminoglycoside acetyltransferase is described, which possesses a wider substrate range than any such enzyme so far discovered in clinical isolates of antibiotic-resistant bacteria. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.6.951
更新日期:1976-06-01 00:00:00
abstract::An ultrasensitive assay utilizing high-pressure liquid chromatography and mass spectrometry detection was developed and validated for the quantification of the antiretrovirals atazanavir (ATV), darunavir (DRV), lopinavir (LPV), ritonavir (RTV), and efavirenz (EFV) in human mononuclear cell (MNC) extracts. The assay ut...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02551-13
更新日期:2014-05-01 00:00:00
abstract::Human cytomegalovirus (HCMV) infection does not generally cause problems in the immunocompetent adult but can result in severe clinical disease in the fetus, neonate, and immunocompromised host. Ganciclovir (GCV), the agent currently used to treat most HCMV infections, has resulted in much therapeutic success; however...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1506-1511.2000
更新日期:2000-06-01 00:00:00
abstract::Fifty strains of Mycoplasma pneumoniae in L cells were tested for susceptibility to macrolide antibiotics. Rokitamycin, a new macrolide antibiotic, was most active against these organisms, with an MIC for 90% of strains of 0.007 microgram/ml. The MICs of erythromycin, josamycin, and kitasamycin for 90% of strains were...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1843
更新日期:1987-11-01 00:00:00
abstract::Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which may be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited greater than 90% of 352 bacterial isolates representing ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1235
更新日期:1991-06-01 00:00:00
abstract::The post-β-lactamase-inhibitor effect (PBLIE) of tazobactam combined with ceftolozane was evaluated by time-kill assays on two clinical Escherichia coli strains producing CTX-M-15 with or without TEM-1. The organisms were exposed (2 h) to 4 μg/ml/4 μg/ml of ceftolozane-tazobactam (4× MIC), 4 μg/ml of ceftolozane, and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02398-13
更新日期:2014-01-01 00:00:00
abstract::PER-1 extended-spectrum β-lactamase-producing Gram-negative bacilli are resistant to oxyimino-cephalosporins. However, the bla(PER-1) gene has never been reported in Klebsiella pneumoniae. Here, we studied interspecies dissemination of the bla(PER-1) gene by horizontal transfer of Tn1213 among Acinetobacter baumannii,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00994-10
更新日期:2011-03-01 00:00:00
abstract::Most manifestations of candidiasis are associated with biofilm formation on biological or inanimate surfaces. Candida albicans biofilms are recalcitrant to treatment with conventional antifungal therapies. Here we report on the activity of caspofungin, a new semisynthetic echinocandin, against C. albicans biofilms. Ca...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3591-3596.2002
更新日期:2002-11-01 00:00:00
abstract::The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.5.532
更新日期:1975-11-01 00:00:00
abstract::In this paper we provide the first biochemical evidence of the existence of a family of structure-related antimicrobial peptides, the siderophore-microcins, in the Enterobacteriaceae family. We isolated and characterized two novel siderophore-microcins, MccM and MccH47, previously characterized through genetic studies...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00744-09
更新日期:2010-01-01 00:00:00
abstract::Berberine sulfate is an alkaloid extracted from the roots and bark of various plants and possesses antibacterial, antifungal, and antiprotozoal activities. Most studies have focused on the bacteriostatic or bactericidal activities of this compound. In this study, we report that berberine sulfate is bacteriostatic for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.9.1370
更新日期:1988-09-01 00:00:00
abstract::We compared the kinetics of amphotericin B (AMB) lung accumulation and fungal clearance by liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) in a neutropenic murine model of invasive pulmonary mucormycosis (IPM). Immunosuppressed BALB/c mice were inoculated with 1 x 10(6) Rhizopus oryzae spores ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01222-09
更新日期:2010-03-01 00:00:00