scholarly journals In Vitro Activity of Daptomycin against Vancomycin-Resistant Enterococci of Various Van Types and Comparison of Susceptibility Testing Methods

2003 ◽  
Vol 47 (12) ◽  
pp. 3760-3763 ◽  
Author(s):  
James H. Jorgensen ◽  
Sharon A. Crawford ◽  
Cynthia C. Kelly ◽  
Jan E. Patterson

ABSTRACT The increasing prevalence of vancomycin-resistant enterococcal (VRE) infections and the limited number of antimicrobial agents for their treatment emphasize a need for new, more effective agents. In this study, the in vitro activity of daptomycin was determined against a collection of 156 VRE from seven different institutions. Van types were characterized by PCR, and pulsed-field gel electrophoresis was performed to exclude isolates with >85% relatedness by dendrogram. Included were 126 Enterococcus faecium (109 vanA, 17 vanB) isolates, 5 Enterococcus faecalis (3 vanA, 2 vanB) isolates, 2 Enterococcus avium (vanA) isolates, 1 Enterococcus durans (vanA) isolate, 10 Enterococcus gallinarum (vanC1) isolates, and 12 Enterococcus casseliflavus (vanC2) isolates. MICs of daptomycin and five additional agents were determined by the NCCLS broth microdilution method with Mueller-Hinton (MH) broth containing supplemental calcium. MICs were also determined using two investigational E-test strip formulations, and disk diffusion testing was performed by the standard NCCLS method. The MIC of daptomycin at which 50% of the isolates tested were inhibited for this isolate collection was 4 μg/ml, and the MIC at which 90% of the isolates tested were inhibited was 8 μg/ml. Two isolates of vanA E. faecium were resistant to linezolid, and one isolate was resistant to quinupristin-dalfopristin. MICs of daptomycin determined by the E test with and without added calcium varied by 8- to 16-fold, and disk diffusion zones varied by 3 to 6 mm according to the calcium content of the commercial MH agar lots used in the study. This study has shown daptomycin to have good activity against a diverse collection of contemporary VRE isolates. However, improved standardization of the calcium content of MH agar will be important for reliable testing of daptomycin by clinical laboratories using either the E test or disk diffusion methods.

1988 ◽  
Vol 8 (4) ◽  
pp. 277-279
Author(s):  
Wendy L. Vaudry ◽  
Claudia Gratton ◽  
Kinga Kowalewska ◽  
Wanda M. Wenman

The minimum inhibitory concentration (MIC) of daptomycin was compared with that of four other antimicrobial agents against clinically relevant staphylococci. Sixtyfive isolates were obtained from patients on continuous ambulatory peritoneal dialysis (CAPD) who contracted peritonitis. These isolates comprised 29 S. Sureus strains (all sensitive to oxacillin); 25 S. epidermidis strains (14 sensitive and 9 resistant to oxacillin); and 11 unspeciated coagulase-negative staphylococci (2 sensitive and 11 resistant to oxacillin). All of the oxacillin susceptible strains were inhibited by ≤2 mg/L of the five antibiotics tested. The oxacillin resistant staphylococci were also resistant to cefuroxime and variably resistant to cefamandole, but were uniformly susceptible to both vancomycin and daptomycin. Daptomycin possesses equivalent in vitro activity to vancomycin against strains of S. Sureus and coagulase negative staphylococci associated with CAPD peritonitis. If vancomycin resistance becomes a significant problem in these patients, and daptomycin is shown to be active against vancomycin resistant organisms, then it would have potential usefulness as an alternative to vancomycin in the treatment of peritonitis caused by multiply -resistant staphylococci.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S310-S311 ◽  
Author(s):  
Olga Lomovskaya ◽  
Jill Lindley ◽  
Debora Rubio-Aparicio ◽  
Kirk J Nelson ◽  
Mariana Castanheira

Abstract Background QPX7728 (QPX) is a novel broad-spectrum boron-containing inhibitor of serine- and metallo-β-lactamases (MBLs). We evaluated the in vitro activity of QPX combined with several β-lactams against carbapenem-resistant AB (CRAB) and PSA clinical isolates with varying β-lactam resistance mechanisms. Methods A total of 503 CRAB (meropenem [MEM] MIC ≥8 µg/mL) and 762 PSA clinical isolates were tested by the reference broth microdilution method against β-lactams alone and combined with QPX (4 µg/mL and 8 µg/mL). PSA isolates were selected to represent the normal distribution of MEM, ceftazidime–avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance according to 2017 surveillance data (representative panel). Additionally, 262 PSA isolates that were either nonsusceptible (NS) to MEM (MIC, ≥4 µg/mL) or to TOL-TAZ (MIC, ≥8 µg/mL), or resistant (R) to CAZ-AVI (MIC, ≥16 µg/mL) (challenge panel) were also tested. Within this 262 strain challenge set, 56 strains carried MBLs and the majority also had nonfunctional OprD. Results Against CRAB, QPX at 4 and 8 µg/mL increased the potency of all β-lactams tested. MEM-QPX was the most potent combination (table) displaying MIC50/MIC90 at 1/8 and 0.5/4 µg/mL with QPX at fixed 4 and 8 µg/mL, respectively. Susceptibility (S) to MEM was restored in >95% of strains. Against the 500 PSA from the representative panel, S for all QPX combinations was >90%. For the challenge panel, TOL-QPX and piperacillin (PIP)-QPX were the most potent combinations, restoring S in 76–77% of strains. TOL-QPX and MEM-QPX or cefepime (FEP)-QPX restored the MIC values to S rates when applying the CLSI breakpoint for the compound alone (comparison purposes only) in ~90% and ~75% of non-MBL-producing strains, respectively, vs. 60–70% for TOL-TAZ and CAZ-AVI. PIP-QPX reduce the MIC values to S values for PIP-TAZ in ~60% of MBL-producing strains vs. 20–30% and 3–7% for other QPX combinations and non-QPX tested combinations, respectively. Conclusion Combinations of QPX with various β-lactam antibiotics displayed potent activity against CRAB and resistant PSA isolates and warrant further investigation. Disclosures All authors: No reported disclosures.


1997 ◽  
Vol 41 (5) ◽  
pp. 1156-1157 ◽  
Author(s):  
O Uzun ◽  
S Kocagöz ◽  
Y Cetinkaya ◽  
S Arikan ◽  
S Unal

The in vitro activity of LY303366, a new echinocandin derivative, was evaluated with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of the isolates were inhibited were 0.125 microg/ml for Candida albicans and C. tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0 microg/ml for C. parapsilosis.


1996 ◽  
Vol 40 (9) ◽  
pp. 2142-2146 ◽  
Author(s):  
K V Singh ◽  
T M Coque ◽  
B E Murray

The in vitro activity of the trinem sanfetrinem (formerly GV104326) (GV) was compared with that of vancomycin, ampicillin, and/or nafcillin against 287 gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and multiresistant enterococci, by the agar and microbroth dilution methods. GV demonstrated 2 to 16 times more activity than ampicillin and nafcillin against the majority of these organisms. The MIC range of GV was 16 to 64 micrograms/ml for 19 Enterococcus faecium strains that were highly resistant to ampicillin (ampicillin MIC range, 64 to 512 micrograms/ml) and vancomycin resistant and 0.25 to 32 micrograms/ml for resistant Rhodococcus spp. Similar activities (+/-1 dilution) were observed by either the agar or the broth microdilution method. GV demonstrated bactericidal activity against a beta-lactamase-producing Enterococcus faecalis strain and against two methicillin-susceptible Staphylococcus aureus strains in 10(5)-CFU/ml inocula. Synergy between GV and gentamicin was observed against an E. faecalis strain that lacked high-level gentamicin resistance. The activity of GV suggests this compound warrants further study.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S375 ◽  
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Jennifer M Streit ◽  
Leonard R Duncan ◽  
Robert K Flamm

Abstract Background Zidebactam (ZID), a bicyclo-acyl hydrazide, is a β-lactam enhancer with a dual mechanism of action involving selective and high binding affinity to Gram-negative (GN) PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime (FEP) combined with ZID against GN organisms causing bloodstream infections (BSI) in hospitals worldwide. Methods A total of 2,094 isolates from 105 medical centers were evaluated. Isolates were collected from Europe (1,050), USA (331), Latin America (LA; 200) and the Asia-Pacific region (AP; 393) in 2015, and China (120) in 2013 by the SENTRY Program. Susceptibility (S) testing was performed by reference broth microdilution method against FEP-ZID (1:1 ratio) and comparators. The collection included 1,809 Enterobacteriaceae (ENT), 170 P. aeruginosa (PSA) and 115 Acinetobacter spp. (ASP). Results FEP-ZID was very active against ENT (MIC50/90 of ≤0.03/0.12 μg/mL) with 99.9 and 100.0% of isolates inhibited at ≤4/4 and ≤8/8 μg/mL, respectively, and retained potent activity against carbapenem-resistant (CRE; n = 44; MIC50/90, 1/4 μg/mL), multidrug-resistant (MDR), and extensively drug-resistant (XDR) isolates (Table). Amikacin (AMK; MIC50/90, 2/4 μg/mL; 97.7% S) was also very active against ENT, and colistin (COL; MIC50/90, 0.12/>8 μg/mL) inhibited only 87.3% of isolates at ≤2 μg/mL. FEP-ZID was highly active against PSA, including isolates resistant to other antipseudomonal β-lactams, MDR (MIC50/90, 4/8 μg/mL) and XDR (MIC50/90, 4/8 μg/mL) isolates. Among the comparators, COL (MIC50/90 of ≤0.5/1 μg/mL; 100.0% S) and AMK (MIC50/90, 4/16 μg/mL; 91.2% S) were the most active agents against PSA. FEP-ZID (MIC50/90, 16/32 μg/mL) was 4-fold more active than FEP against ASP. Conclusion FEP-ZID (WCK 5222) exhibited potent in vitro activity against a large worldwide collection of GN isolates from BSI, including MDR and XDR isolates. These results support further clinical development of WCK 5222 for treating BSI. Disclosures H. S. Sader, Wockhardt Bio Ag: Research Contractor, Research grant; M. Castanheira, Wockhardt Bio Ag: Research Contractor, Research grant; J. M. Streit, Wockhardt Bio Ag: Research Contractor, Research grant; L. R. Duncan, Wockhardt Bio Ag: Research Contractor, Research grant; R. K. Flamm, Wock: Research Contractor, Research support


2019 ◽  
Author(s):  
H. Selcuk Ozger ◽  
Tugba Cuhadar ◽  
Serap Suzuk Yildiz ◽  
Zehra Demirbas Gulmez ◽  
Murat Dizbay ◽  
...  

AbstractThe synergistic activity of eravacycline in combination with colistin on carbapenem-resistant A.baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory concentrations (MICs) of eravacycline and colistin were determined by the broth microdilution method. MICs values ranged between 1 to 4 mg and 0,5 to 128 mg/L for eravacycline and colistin, respectively. In-vitro synergy between eravacycline and colistin was evaluated by using the chequerboard methodology. Synergistic activity was found in 10 % of the strains, and additive effect in 20 %. No antagonism was detected. Similar activity was also observed in colistin resistant CRAB isolates. The result of this study indicates that eravacycline and colistin combination may be a potential therapeutic option for the treatment of CRAB related infections.


2021 ◽  
Vol 23 (1) ◽  
pp. 92-99
Author(s):  
Nataly V. Ivanchik ◽  
Мarina V. Sukhorukova ◽  
Аida N. Chagaryan ◽  
Ivan V. Trushin ◽  
Andrey V. Dekhnich ◽  
...  

Objective. To determine in vitro activity of thiamphenicol and other clinically available antimicrobials against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. Materials and Methods. We included in the study 875 clinical isolates from 20 Russian cities during 2018–2019. Among tested strains, 126 were H. influenzae, 389 – S. pneumoniae, 360 – S. pyogenes. Antimicrobial susceptibility testing was performed using broth microdilution method according to ISO 20776-1:2006. AST results were interpreted according to EUCAST v.11.0 clinical breakpoints. Results. The minimum inhibitory concentrations (MICs) of thiamphenicol did not exceed 2 mg/L for 94.4% of H. influenzae strains (MIC50 and MIC90 were 0.5 and 1 mg/L, respectively). Thiamphenicol was active against 76.9% of ampicillin-resistant H. influenzae strains (MIC of thiamphenicol < 2 mg/L). The MIC of thiamphenicol was in the range of 0.06–2 mg/L for 96.7% of S. pneumoniae strains (MIC50 and MIC90 were 0.5 and 2 mg/L, respectively). The MIC of thiamphenicol for 90.6% of S. pneumoniae strains with reduced susceptibility to penicillin (MIC of penicillin > 0.06 mg/L) did not exceed 2 mg/L. A total of 88.1% of S. pneumoniae strains resistant to erythromycin were highly susceptible to thiamphenicol (MIC < 2 mg/L). The MIC of thiamphenicol did not exceed 8 mg/L for 96.1% of S. pyogenes strains (MIC50 and MIC90 were 2 and 4 mg/L, respectively). Conclusions. Thiamphenicol was characterized by relatively high in vitro activity, comparable to that of chloramphenicol, against tested strains of H. influenzae, S. pneumoniae and S. pyogenes, including S. pneumoniae isolates with reduced susceptibility to penicillin.


2000 ◽  
Vol 44 (5) ◽  
pp. 1242-1246 ◽  
Author(s):  
Angela M. Nilius ◽  
Patti M. Raney ◽  
Dena M. Hensey-Rudloff ◽  
Weibo Wang ◽  
Qun Li ◽  
...  

ABSTRACT A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as Candida albicans, Candida tropicalis, and Candida glabrata, as well as less commonly encounteredCandida species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against Candida strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against Cryptococcus neoformans was comparable to its activity against Candida spp. However, A-192411.29 did not demonstrate complete growth inhibition ofAspergillus fumigatus by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S321-S321
Author(s):  
Laura M Koeth ◽  
Jeanna M DiFranco-Fisher ◽  
Nicole Scangarella-Oman

Abstract Background Gepotidacin (GSK2140944) is a first in class novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in clinical development for the treatment of gonorrhea and uncomplicated UTI (acute cystitis). Gepotidacin selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism not utilized by any currently approved therapeutic agent and demonstrates in vitro activity against most target pathogens resistant to established antibacterials, including fluoroquinolones. This study was undertaken to determine the effect of various urine parameters on the in vitro activity of gepotidacin and a comparative agent, levofloxacin, against a variety of bacteria. Methods Study strains were tested according to the reference CLSI broth microdilution method using cation-adjusted Mueller–Hinton broth (CAMHB) and the following method variations: CAMHB with 25%, 50%, and 100% urine (not pH adjusted) and 100% urine (pH adjusted to 7.2–7.4, and 8). Quality control strains were concurrently tested each day. Results MIC endpoints in the reference method and in 100% urine were easily determined (i.e., clear buttons of growth up to the first well of no growth). Gepotidacin MIC results are summarized in the table. For E. coli and S. saprophyticus, there was a trend for higher gepotidacin MIC results with the addition of increasing amounts of urine. However, the increase was minimal such that mean dilution differences were ≤ 1.54. Against S. epidermidis, gepotidacin MICs were not significantly impacted by the addition of urine as 100% of urine condition MICs were within ±1 doubling dilution of the reference method MIC. The gepotidacin results for E. coli indicate that the average 1–2 dilution MIC increase observed in the unadjusted 100% pooled urine MIC may be associated with lower pH. A similar increase in levofloxacin MIC results for E. coli were also associated with pH, but at the higher pH of 8.0. In contrast, the increase in MIC observed in both the gepotidacin and levofloxacin S. saprophyticus results in 100% pooled urine do not appear to be a function of pH. Conclusion Overall, the effect of urine on the gepotidacin and levofloxacin MICs was minimal and not inclusive of all strains tested. Disclosures All authors: No reported disclosures.


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