In vitro activity of ampicillin and ceftriaxone against ampicillin-susceptible Enterococcus faecium

2019 ◽  
Vol 74 (8) ◽  
pp. 2269-2273 ◽  
Author(s):  
Michael P Lorenzo ◽  
James M Kidd ◽  
Stephen G Jenkins ◽  
David P Nicolau ◽  
Seth T Housman

AbstractObjectivesTo assess activity of the combination of ceftriaxone and ampicillin against clinical isolates of ampicillin-susceptible Enterococcus faecium.MethodsAmpicillin-susceptible E. faecium (n = 29) and Enterococcus faecalis (n = 10) collected from locations in the USA and France were used for this analysis. Susceptibility testing was performed by gradient diffusion strip (GDS) and broth microdilution (BMD). Synergy with the combination of ceftriaxone and ampicillin was assessed in all isolates using GDS crossing and double disc diffusion methods. Selected isolates (nine E. faecium and three E. faecalis) were assessed for synergy in time–kill studies using ampicillin alone and in combination with ceftriaxone.ResultsIn isolates of E. faecium, the median (range) ampicillin MIC by BMD was 0.5 (0.25–4) mg/L and by GDS it was 2 (1–8)  mg/L. In E. faecalis, the median (range) ampicillin MIC by BMD was 0.5 (0.5–1) mg/L and by GDS it was 2 (0.75–3) mg/L. A total of 24/29 (82.8%) isolates of E. faecium displayed synergy by GDS and 22/29 (75.9%) by double disc diffusion. Seven of 10 (70%) isolates of E. faecalis displayed synergy by GDS and 4/10 (40%) by double disc diffusion. Time–kill studies found synergy in 3/9 (33.3%) E. faecium and 3/3 (100%) E. faecalis.ConclusionsIn contrast to the demonstrated synergy in time–kill models of ceftriaxone and ampicillin for E. faecalis, this combination does not appear to provide uniform synergy in E. faecium. Antagonism was not observed. Clinical correlation is necessary and caution should be used when considering ampicillin and ceftriaxone for the treatment of infections caused by ampicillin-susceptible E. faecium.

2019 ◽  
Author(s):  
lanfang guo ◽  
Dandan Yin ◽  
Yan Guo ◽  
Yonggui Zheng ◽  
Qingyu Shi ◽  
...  

Abstract Objective: To evaluate ampicillin to predict activity of Enterococcus faecalis and Enterococcus faecium to imipenem. Methods: A total of 127 non-duplicated strains of Enterococcus faecalis and 124 strains of Enterococcus faecium were collected from 23 hospitals in China. The antimicrobial susceptibility testing was determinated using broth microdilution and disk diffusion. Results: For all E. faecalis , when using penicillin/ampicillin results to predict susceptibility to imipenem (called as penicillin-imipenem prediction mode and amipicillin-imipenem mode), the categorical agreement (CA) and major error (ME) rate was 88.9%/95.3% and 6.3%/0%, whereas it was 89.7%/96.8% and 8.7%/1.6%, when using that results of disk diffusion, respectively. No very major error (VME) rate was founded for both prediction modes. For penicillin susceptible, ampicillin susceptible E. faecalis , the CA rate of ampicillin-imipenem prediction mode based on results from broth microdilution and disk diffusion to was both 100%, and neither was founded with VME or ME rate. For penicillin resistant, ampicillin susceptible E. faecalis , the CA rate of ampicillin-imipenem prediction mode based on results from broth microdilution and disk diffusion was 57.1% and 81.8%, respectively. And neither was founded with VME or ME rate. For penicillin resistant, ampicillin resistant E. faecalis , the CA/ME/VME rate of ampicillin-imipenem prediction mode based on results from broth microdilution and disk diffusion was 100%/0%/0% and 77.8%/22.2%/0%, respectively. For all E. faecium , the CA rate of penicillin-imipenem and ampicillin-imipenem prediction mode based on results from broth microdilution was 100% and 99.2%, and it was both 99.2% based on results from disk diffusion. ME and VME rate for all four prediction modes was 0%. For penicillin resistant, ampicillin resistant E. faecium , the CA rate was 100%, as well as penicillin susceptible, ampicillin susceptible E. faecium . None of prediction mode was found with ME or VME rate. Conclusion: For penicillin susceptible, ampicillin susceptible or penicillin resistant, ampicillin resistant E. faecalis and E. faecium , ampicillin susceptibility results of broth microdilution could accurately predict in vitro activity of imipenem. However, for penicillin resistant, ampicillin susceptible E. faecalis and E. faecium , using ampicillin results to predict imipemem susceptibility of was poorly consistent.


Author(s):  
Ka Lip Chew ◽  
Sophie Octavia ◽  
Joelle Go ◽  
Sally Ng ◽  
Yit Er Tang ◽  
...  

Abstract Objectives To determine the in vitro susceptibility of members of the Mycobacterium abscessus complex to routinely tested antibiotics and to an extended antibiotic panel. Methods Non-duplicate isolates for which susceptibility testing results were available were included in this study. Retrospective laboratory records were reviewed, including tigecycline susceptibility results, and testing was performed with additional drugs, including vancomycin, dalbavancin, telavancin, oritavancin, rifabutin, delafloxacin, eravacycline, clofazimine and bedaquiline using broth microdilution (Sensititre, Thermo Fisher). Results A total of 218 M. abscessus complex isolates were included for retrospective review, of which 151 were respiratory isolates. Of these 218 isolates, 211 were available for additional testing with the extended antibiotic panel. Of these, 146 were respiratory isolates. One isolate had a vancomycin MIC of 2 mg/L and MICs of all other isolates were >8 mg/L. All isolates had MICs of >8 mg/L for oritavancin, dalbavancin and telavancin. One isolate had a delafloxacin MIC of 4 mg/L and MICs of all other isolates were >8 mg/L. The MIC50/MIC90s of rifabutin, tigecycline, eravacycline, clofazimine and bedaquiline were 16/32, 0.5/1, 0.12/0.25, 0.12/0.25 and 0.06/0.12 mg/L, respectively. Conclusions In vitro activity was demonstrated for clofazimine, bedaquiline and eravacycline, indicating potential for inclusion as standardized therapy for M. abscessus complex infections.


Author(s):  
Bertrand Nyuykonge ◽  
Lukas van Amelsvoort ◽  
Kimberly Eadie ◽  
Ahmed H. Fahal ◽  
Annelies Verbon ◽  
...  

For many fungal infections, in vitro susceptibility testing is used to predict if an isolate is resistant or susceptible to the antifungal agent used to treat the fungal infection. For Madurella mycetomatis , the main causative agent of mycetoma, in vitro susceptibility testing currently is not performed on a routine basis. The current in vitro susceptibility testing method is labor intensive and sonication must be done to generate a hyphal inoculum. For endpoint visualization, expensive viability dyes are needed. Here we investigated if the currently used in vitro susceptibility method could be adapted to make it amendable for use in a routine setting which can be used in low income countries, where mycetoma is endemic. First, we developed a methodology in which hyphal fragments can be generated without the need for sonication, by comparing different bead beating methodologies. Next, in vitro susceptibility was assessed using standard broth microdilution assays as well as disc diffusion, E-testing and VIPcheck™ methodologies. We demonstrate that after a hyphal suspension is generated by glass bead beating, disc diffusion, E-testing and VIPcheck™ can be used to determine susceptibility towards itraconazole, posaconazole and voriconazole of Madurella mycetomatis . The MICs found with the E-test were comparable to those obtained with our modified CLSI-based broth microdilution in vitro susceptibility assay for itraconazole and posaconazole. Furthermore, we found an inverse relationship between the zone of inhibition and MIC obtained with E-test and the modified CLSI broth microdilution technique.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Christian Wallmüller ◽  
Herold Birger ◽  
Fritz Sterz ◽  
Athanasios Makristathis ◽  
Michael Ramharter

Aim: Infections are a common problem in cardiac arrest survivors. Antimicrobial drugs are often administered in routine care during treatment of patients with mild therapeutic hypothermia. Since there is to date no evidence for the pharmacodynamics of antimicrobial drugs under mild therapeutic hypothermia conditions, we investigated the in vitro activity of common antimicrobials against clinically relevant bacterial pathogens. Methods: Activities of antimicrobial drugs against clinically relevant bacterial pathogens were assessed in vitro by disc diffusion and broth microdilution assays at normothermic (37°C) and hypothermic (32°C) conditions. Results: 73 bacterial isolates were tested in disc diffusion and 15 in broth microdilution assays. Mean differences in zone diameters and minimal inhibitory concentration ratios were 0.6 mm (95% confidence interval: 0.3-0.9 mm) and 0.98; (95% confidence interval: 0.95 - 1.02), respectively, meeting predefined criteria for equivalence of in vitro antimicrobial activity. Conclusion: The presented data provide reassuring evidence that the intrinsic activity of antimicrobials seems to be unaltered in mild therapeutic hypothermia. However, further studies evaluating the pharmacokinetics including target site concentrations of the respective drugs and in vivo pharmacodynamics are necessary to complement our understanding of the appropriate use of antimicrobials in mild therapeutic hypothermia


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S370-S371
Author(s):  
Jun Oh ◽  
Maria Traczewski ◽  
Raymond Schuch

Abstract Background CF-301 is a novel, recombinantly-produced bacteriophage-derived lysin (cell wall hydrolase) and is the first agent of this class in the US to enter into clinical development for the treatment of bacteremia including endocarditis due to S. aureus. Hallmark features of CF-301 include rapid and pathogen-specific bacteriolytic activity, synergy with antibiotics, biofilm-disrupting activity, a low propensity for resistance, and the capacity to suppress antibiotic resistance. This is the first report of an international surveillance study for CF-301. Methods 349 methicillin-sensitive and –resistant S. aureus (MSSA and MRSA, respectively) isolates were collected from various infection sources at multiple hospitals from 2015–2017 throughout the US, Greece, Hungary and Italy. In addition to the contemporary isolates, a set of 149 MSSA and MRSA clinical isolates from 2011 were also obtained from US hospital sources. MICs for CF-301 were determined using a new antimicrobial susceptibility testing (AST) medium for broth microdilution recently endorsed by Clinical and Laboratory Standards Institute (CLSI) for use with CF-301. The testing medium consists of cation-adjusted Muller Hinton Broth supplemented with 25% horse serum and 0.5 mM DTT (CAMHB-HSD). Susceptibility to conventional antibiotics was also examined in this study using standard methodology (CLSI document M07-A10) and included: vancomycin, trimethoprim-sulfamethoxazole, daptomycin, oxacillin, linezolid, clindamycin, and cefazolin. Results CF-301 had MIC50, MIC90, and MIC100 values of 0.5, 1, and 2 μg/mL, respectively, against each set of contemporary MSSA (n = 176) and MRSA (n = 173) clinical isolates. There were no differences noted with respect to the geographic source (in the US and Europe) of isolates. Furthermore, the CF-301 MICs reported here for 2015–2017 isolates were identical to that observed for MSSA and MRSA isolates from 2011. Conclusion CF-301 demonstrated potent in vitro activity against a total of 498 clinical S. aureus isolates from a range of human infections (including bacteremia) and different geographies. Contemporary clinical isolates did not demonstrate reduced susceptibility to CF-301 compared with the 2011 isolates. Disclosures J. Oh, ContraFect Corp: Employee, Salary; R. Schuch, ContraFect Corp: Employee, Salary


2019 ◽  
Vol 75 (2) ◽  
pp. 384-391 ◽  
Author(s):  
Iris Spiliopoulou ◽  
Krystyna Kazmierczak ◽  
Gregory G Stone

Abstract Objectives To report data for ceftazidime/avibactam and comparators against meropenem-non-susceptible Enterobacteriaceae collected globally (excluding centres in the USA) from 2015 to 2017 as part of the International Network For Optimal Resistance Monitoring (INFORM) surveillance programme. Methods MICs and susceptibility were determined using EUCAST broth microdilution methodology and EUCAST breakpoints. Isolates were screened to detect genes encoding β-lactamases using multiplex PCR assays. MBL-positive isolates were those in which one or more of the IMP, VIM and/or NDM genes were detected. Results A total of 1460 meropenem-non-susceptible isolates were collected and, of the agents on the panel, susceptibility was highest to ceftazidime/avibactam, colistin and tigecycline [73.0%, 77.0% (1081/1403) and 78.1%, respectively]. Ceftazidime/avibactam was not active against MBL-positive isolates (n=367); these isolates showed the highest rates of susceptibility to colistin (92.1%, 303/329), tigecycline (71.9%) and amikacin (46.6%). A total of 394 isolates were resistant to ceftazidime/avibactam and, of the 369 isolates that were screened, 98.4% were found to carry a gene encoding an MBL enzyme. Among isolates that were identified as carbapenemase positive and MBL negative (n=910), susceptibility was highest to ceftazidime/avibactam (99.8%). Susceptibility was also highest to ceftazidime/avibactam among isolates that were carbapenemase negative and MBL negative (94/98, 95.9%). Conclusions These data highlight the need for continued surveillance of antimicrobial activity as well as the need for new antimicrobials to treat infections caused by meropenem-non-susceptible Enterobacteriaceae, for which the options are extremely limited.


2004 ◽  
Vol 48 (9) ◽  
pp. 3305-3311 ◽  
Author(s):  
Jeff Powis ◽  
Allison McGeer ◽  
Karen Green ◽  
Otto Vanderkooi ◽  
Karl Weiss ◽  
...  

ABSTRACT Empirical treatment is best guided by current surveillance of local resistance patterns. The goal of this study is to characterize the prevalence of antimicrobial nonsusceptibility within pneumococcal isolates from Canada. The Canadian Bacterial Surveillance Network is comprised of laboratories from across Canada. Laboratories collected a defined number of consecutive clinical and all sterile site isolates of S. pneumoniae in 2002. In vitro susceptibility testing was performed by broth microdilution with NCCLS guidelines. Rates of nonsusceptibility were compared to previously published reports from the same network. A total of 2,539 isolates were tested. Penicillin nonsusceptibility increased to 15% (8.5% intermediate, 6.5% resistant) compared to 12.4% in 2000 (P ≤ 0.025, χ2). Only 32 (1.3%) isolates had an amoxicillin MIC of ≥4 μg/ml and only 2 of 32 cerebrospinal fluid isolates had an intermediate susceptibility to ceftriaxone by meningeal interpretive criteria (MIC = 1 μg/ml). A total of 354 (13.9%) isolates were macrolide nonsusceptible (46.3% MLSB, 56.7% M phenotype), increasing from 11.4% in 2000 (P ≤ 0.0075, χ2). Only 13 (<1%) isolates had a telithromycin MIC of >1 μg/ml. Ciprofloxacin nonsusceptibility (defined as an MIC of ≥4 μg/ml) increased to 2.7% compared to 1.4% in 2000 (P ≤ 0.0025, χ2) and was primarily found in persons ≥18 years old (98.5%). Nonsusceptibility to penicillin, macrolides, and fluoroquinolones is increasing in Canada. Nonsusceptibility to amoxicillin and ceftriaxone remains uncommon. Newer antimicrobials such as telithromycin and respiratory fluoroquinolones have excellent in vitro activity.


1999 ◽  
Vol 43 (11) ◽  
pp. 2776-2779 ◽  
Author(s):  
S. O. Matsumura ◽  
L. Louie ◽  
M. Louie ◽  
A. E. Simor

ABSTRACT Using checkerboard and time-kill assays, we evaluated the in vitro activity of quinupristin-dalfopristin (RP 59500) alone and in combination with five other antimicrobial agents against 12 clinical strains of vancomycin-resistant Enterococcus faecium(VREF). In time-kill studies, six VREF strains exhibited synergism with the combination of quinupristin-dalfopristin and doxycycline and three exhibited synergism with quinupristin-dalfopristin plus ampicillin-sulbactam. Combinations of quinupristin-dalfopristin with these and other agents warrant further clinical evaluation for the treatment of serious VREF infections.


1997 ◽  
Vol 41 (6) ◽  
pp. 1307-1312 ◽  
Author(s):  
R C Mercier ◽  
H H Houlihan ◽  
M J Rybak

The objectives of the present study were to compare the in vitro activity of LY333328 (LY) to that of vancomycin (V) alone and in combination with gentamicin (G) and rifampin (R) against methicillin-resistant Staphylococcus aureus (MRSA) and V-resistant Enterococcus faecium (VREF), by using the killing curve methods. In addition, the effect of the inoculum size and protein on LY's activity was evaluated by using MICs and killing curves. MICs, MBCs, and killing curves were determined with supplemented Mueller-Hinton broth (B), B with albumin (4 g/dl) (A), and B with 50% pooled human serum (S). For MRSA, time to 99.9% killing after exposure to LY at four times the MIC (4x MIC) was achieved at 0.5 +/- 0 h (mean +/- standard deviation) and was significantly faster than that by V (8.54 +/- 0.10 h; P = 0.001). Against VREF, LY decreased the inoculum by 2.2 log10 CFU/ml at 24 h (P = 0.002). With a large inoculum of MRSA, the activity of LY and V at 4x MIC was decreased compared to that with the standard inoculum (P = 0.0003) and regrowth occurred at 24 h. The reduction in the number of CFU per milliliter at 24 h to 2 log10 CFU/ml was restored by increasing the LY concentration to at least 16x MIC. At 24 h, the combinations of LY and G, LY and R, LY and V, and V and G were better than either LY or V alone against a large inoculum of MRSA (P = 0.0002). LY and G achieved 99.9% killing at 1.01 +/- 0.03 h and was more rapid (P < 0.007) than all the other regimens studied except for V and G, which achieved 99.9% killing at 3.59 +/- 0.01 h. Killing curves determined with different media against a standard inoculum of MRSA did not demonstrate a significant difference between LY and V at 24 h. Time to 99.9% killing was more rapid with LY than with V in B, A, and S (P = 0.0002). Times to 99.9% killing by LY in B, A, and S were not significantly different from each other. Against VREF, LY killed better than V in B, A, or S at 24 h (P = 0.0002). LY in B was more active than LY in A or S (P = 0.0002). LY is a new potent glycopeptide with a unique activity profile. It has a greater activity than that of V against MRSA and has activity against VREF. LY demonstrated synergism in combination with gentamicin against MRSA. LY was affected by large inoculum sizes and proteins in time-kill studies. However, the effect was compensated for by increasing the drug concentration to 16x MIC.


2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Natalie S. Nunnally ◽  
Kizee A. Etienne ◽  
David Angulo ◽  
Shawn R. Lockhart ◽  
Elizabeth L. Berkow

ABSTRACT Ibrexafungerp is a first-in-class glucan synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, or micafungin) by broth microdilution. Results for ibrexafungerp were compared with those for each echinocandin. Ibrexafungerp had good activity against all echinocandin-resistant C. glabrata isolates.


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