scholarly journals MIC and time-kill studies of antipneumococcal activity of GV 118819X (sanfetrinem) compared with those of other agents.

1997 ◽  
Vol 41 (1) ◽  
pp. 148-155 ◽  
Author(s):  
S K Spangler ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
United States ◽  
The United States ◽  
Broth Microdilution ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Amoxicillin Clavulanate ◽  
Agar Dilution ◽  
Resistant Strains ◽  
Time Kill

Agar dilution MIC methodology was used to test the activities of GV 118819X (sanfetrinem), ampicillin, amoxicillin, amoxicillin-clavulanate, cefpodoxime, loracarbef, levofloxacin, clarithromycin, ceftriaxone, imipenem, and vancomycin against 53 penicillin-susceptible, 84 penicillin-intermediate and 74 penicillin-resistant pneumococci isolated in the United States. GV 118819X was the most active oral beta-lactam, with MIC at which 50% of the isolates were inhibited (MIC50)/MIC90 values of 0.008/0.03, 0.06/0.5, and 0.5/1.0 micrograms/ml against penicillin-susceptible, -intermediate, and -resistant stains, respectively. Amoxicillin and amoxicillin in the presence of clavulanate (2:1) were the second most-active oral beta-lactams, followed by ampicillin and cefpodoxime; loracarbef was not active against penicillin-intermediate and -resistant strains. Clarithromycin was most active against penicillin-susceptible strains but was less active against intermediate and resistant stains. All pneumococcal stains were inhibited by ceftriaxone and imipenem at MICs of < or = 4.0 and < or = 1.0 micrograms/ml, respectively. The activities of levofloxacin and vancomycin were unaffected by penicillin susceptibility. Time-kill studies of three penicillin-susceptible, three penicillin-intermediate, and three penicillin-resistant pneumococci showed that all compounds, at the broth microdilution MIC, yielded 99.9% killing of all strains after 24 h. Kinetic patterns of all oral beta-lactams, ceftriaxone, and vancomycin were similar relative to the MIC, with 90% killing of all strains first observed after 12 h. However, killing by amoxicillin-clavulanate, imipenem, and levofloxacin was slightly faster and that by clarithromycin was slower than that by the above-described drugs. At 2 x the MIC, more strains were killed earlier than was the case at the MIC, but the pattern seen at the MIC prevailed. When MICs and kill kinetics were combined, sanfetrinem was the most active oral antipneumococcal agent in this study.

scholarly journals Antipneumococcal activity of BAY 12-8039, a new quinolone, compared with activities of three other quinolones and four oral beta-lactams.

1997 ◽  
Vol 41 (12) ◽  
pp. 2786-2789 ◽  
Author(s):  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Beta Lactam ◽  
Beta Lactams ◽  
Agar Dilution ◽  
Resistant Strains

Activities of BAY 12-8039 against 205 pneumococci were tested by agar dilution. MICs (in micrograms per milliliter) at which 50 and 90% of the isolates are inhibited (MIC50s and MIC90s, respectively) were 0.125 and 0.25 (BAY 12-8039), 2.0 and 4.0 (ciprofloxacin and ofloxacin), and 0.25 and 0.5 (sparfloxacin). Beta-lactam MIC50s and MIC90s for penicillin-susceptible, -intermediate, and -resistant strains, in that order, were 0.016 and 0.03, 0.25 and 2.0, and 2.0 and 4.0 (amoxicillin); 0.03 and 0.06, 0.25 and 4.0, and 4.0 and 8.0 (ampicillin); 0.03 and 0.06, 0.5 and 4.0, and 4.0 and 8.0 (cefuroxime); and 0.03 and 0.125, 0.25 and 2.0, and 4.0 and 8.0 (cefpodoxime). At two times their MICs after 24 h, BAY 12-8039, ciprofloxacin, ampicillin, and cefuroxime were uniformly bactericidal (99.9% killing) against 12 strains; other compounds were bactericidal at four times their MICs.

scholarly journals Comparative Activities of Telavancin Combined with Nafcillin, Imipenem, and Gentamicin against Staphylococcus aureus

2013 ◽  
Vol 57 (6) ◽  
pp. 2678-2683 ◽  
Author(s):  
Steven N. Leonard ◽  
Megan E. Supple ◽  
Ronak G. Gandhi ◽  
Meghna D. Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Utility ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Once Daily ◽  
Content Type ◽  
Resistant Strains ◽  
Synergy Test ◽  
Time Kill

ABSTRACTBeta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains ofStaphylococcus aureus, 10 methicillin-susceptibleS. aureus(MSSA), 10 methicillin-resistantS. aureus(MRSA), and 10 heterogeneously vancomycin-intermediateS. aureus(hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in anin vitropharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P≤ 0.002) and were similar to each other (P≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin againstS. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

scholarly journals In vitro activities of beta-lactam-beta-lactamase inhibitor combinations against Stenotrophomonas maltophilia: correlation between methods for testing inhibitory activity, time-kill curves, and bactericidal activity.

1997 ◽  
Vol 41 (12) ◽  
pp. 2612-2615 ◽  
Author(s):  
J L Muñoz Bellido ◽  
S Muñoz Criado ◽  
I García García ◽  
M A Alonso Manzanares ◽  
M N Gutiérrez Zufiaurre ◽  
...  
Keyword(s):  
Clavulanic Acid ◽  
Stenotrophomonas Maltophilia ◽  
Beta Lactamase ◽  
Broth Microdilution ◽  
Beta Lactam ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Agar Dilution ◽  
Time Kill ◽  
Lactamase Inhibitor

The activities of ampicillin, ampicillin-sulbactam, amoxicillin, amoxicillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic acid, piperacillin, piperacillin-tazobactam, aztreonam, and aztreonam-clavulanic against Stenotrophomonas maltophilia strains for which the MICs of penicillins and commercially available beta-lactam-beta-lactamase inhibitor combinations were higher than the breakpoints usually recommended for Pseudomonas aeruginosa in commercially available broth microdilution methods were tested by the agar diffusion, agar dilution, and broth microdilution methods. Time-kill curve studies were performed when discrepancies between these methods were observed. The MICs obtained by the commercially available broth microdilution method, the agar dilution method, and the broth microdilution method were almost identical. Twenty-five percent of the strains tested showed inhibition diameters of > or =15 mm for ticarcillin-clavulanic acid, and 43.7% of the strains tested showed inhibition diameters of > or =18 mm for piperacillin-tazobactam by the agar diffusion method. The time-kill curves for these strains confirmed the results obtained by dilution methods. Aztreonam-clavulanic acid (2:1) at concentrations of < or =16 microg/ml inhibited all of these strains (MIC range, 1 to 16 microg/ml). The time-kill curves confirmed this activity. The addition of piperacillin to this combination did not modify the MICs. The combination aztreonam-clavulanic acid-ticarcillin was two- to fourfold more active than aztreonam-clavulanic acid alone. We studied the inhibitory and bactericidal activities of the two most active combinations (aztreonam-clavulanic acid and aztreonam-clavulanic acid-ticarcillin) against the standard inoculum and 10 and 50 times the standard inoculum. Inoculum modifications did not modify the MICs. Both combinations showed good bactericidal activity against the standard inoculum. With 10 times the standard inoculum, minimum bactericidal concentration (MBC) results were heterogeneous (for 55% of the strains, MBCs were between the MIC and 4-fold the MIC, and for 45% of the strains MBCs were between 8- and >32-fold the MIC). With 50 times the standard inoculum, MBCs were at least 32-fold the MICs for all the strains tested.

scholarly journals Comparative activities of clarithromycin, erythromycin, and azithromycin against penicillin-susceptible and penicillin-resistant pneumococci.

1996 ◽  
Vol 40 (8) ◽  
pp. 1950-1952 ◽  
Author(s):  
L M Ednie ◽  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
United States ◽  
Clinical Trials ◽  
The United States ◽  
The Other ◽  
Agar Dilution ◽  
Resistant Strains

Activities of clarithromycin, erythromycin, and azithromycin against 120 pneumococci from the United States were tested by agar dilution MIC. All three compounds yielded MICs at which 90% of the isolates were inhibited (MIC90S) of < or = 0.125 micrograms/ml against penicillin-susceptible and -intermediate strains, but MIC90S against resistant strains were > 128.0 micrograms/ml. All erythromycin-resistant strains were also resistant to clarithromycin and azithromycin. Clarithromycin yielded MICs which were generally one or two dilutions lower than those of the other two compounds for all strains. The respective bacteriostatic and bactericidal values (micrograms per milliliter) for two susceptible, two intermediate, and two resistant strains were 0.004 to 0.03 and 0.016 to 0.03 (0.004 to 0.03/0.016 to 0.03) (clarithromycin), 0.008 to 0.06/0.016/0.016 to 0.125 (erythromycin), and 0.016 to 0.06/0.03 to 0.125 (azithromycin); clarithromycin yielded the lowest values. All compounds were uniformly bactericidal after 24 h only; erythromycin was bactericidal at eight times the MIC, and azithromycin and clarithromycin were both bactericidal at two time the MIC. The relevance of these in vitro differences requires clarification by clinical trials.

scholarly journals Corrigendum

2017 ◽  
Vol 4 (6) ◽  
pp. 193-193
Keyword(s):  
United States ◽  
The United States ◽  
Original Text ◽  
The European Union ◽  
Broth Microdilution ◽  
Alternative Treatments ◽  
Gram Positive ◽  
Baseline Activity ◽  
Broth Microdilution Method ◽  
Complicated Skin

Das B, Sarkar C, Das D et al. Telavancin: a novel semisynthetic lipoglycopeptide agent to counter the challenge of resistant Gram-positive pathogens. Ther Adv Infect Dis. 2017 Mar; 4(2): 49–73. DOI: 10.1177/2049936117690501 The authors wish to highlight the following corrections, which should have appeared in the original text: 1.  Page 49, Abstract, lines 4–5: Telavancin is approved for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in the United States when alternative treatments are not available. In Russia and Canada, telavancin is approved for both complicated skin and skin-structure infections (cSSSI) and HABP/VABP. 2.  Page 50, right panel, para 2, lines 15–18: Revised per telavancin label based on latest PI and EMA (also pasted below). In the United States, telavancin is approved in adults for the treatment of cSSSI due to susceptible Gram-positive pathogens. In addition, telavancin is approved for HABP/VABP when alternative treatments are not suitable. In Canada and Russia, telavancin is approved for Gram-positive pathogens for the treatment of patients with cSSSI and HABP/VABP. In the European Union, telavancin is approved for the treatment of nosocomial pneumonia, known or believed to be caused by methicillin-resistant Staphylococcus aureus (MRSA) when other alternative medicines are unsuitable. 3.  Page 51, right panel, para 1, lines 1–6: Per the latest (2016) telavancin PI, HABP/VABP indication for telavancin should be included. 4.  Page 51, Figure 1 caption: The hydrophilic nature of telavancin contributes to its half-life. 5.  Page 53, left panel, para “In vitro activity”, lines 5–8: As per the following (newer) article, which states that “Telavancin MIC is 16-32 fold lower than vancomycin against MRSA.” Mendes RE, Flamm RK, Farrell DJ, et al. Telavancin activity tested against Gram-positive clinical isolates from European, Russian and Israeli hospitals (2011–2013) using a revised broth microdilution testing method: redefining the baseline activity of telavancin. J Chemother 2015; 28: 83–88. DOI: 10.1179/1973947815Y.0000000050 6.  Page 53, right panel, para 1, lines 11–16: Per the Mendes et al. (2015) article listed above, telavancin minimum inhibitory concentration (MIC) is 16- to 32-fold lower than vancomycin against MRSA. 7.  Page 54, Table 1: These MIC values were estimated using old methods. Revise the MIC values based on the references for new MIC methods (see below). Farrell DJ, Mendes RE, Rhomberg PR, et al. Revised reference broth microdilution method for testing telavancin: effect on MIC results and correlation with other testing methodologies. Antimicrob Agents Chemother 2014; 58(9): 5547–5551. DOI: 10.1128/AAC.03172-14 8.  Page 61, right panel, para “ATTAIN trials (ATTAIN 1 and 2)”, lines 9–12: The ATTAIN trials did not include patients with “healthcare-associated pneumonia,” therefore, any mention of this is not correct.

scholarly journals Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening

2018 ◽  
Author(s):  
María Pilar Arenaz Callao ◽  
Rubén González del Río ◽  
Ainhoa Lucía Quintana ◽  
Charles J. Thompson ◽  
Alfonso Mendoza-Losana ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Amoxicillin Clavulanate ◽  
Low Toxicity ◽  
Potential Use ◽  
Ulcer Treatment

ABSTRACTThe potential use of clinically approved beta-lactams for Buruli ulcer (BU) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans. Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibiotics currently used to treat BU, i.e. rifampicin and clarithromycin; this activity was further potentiated in the presence of the beta-lactamase inhibitor clavulanate. In addition, quadruple combinations of rifampicin, clarithromycin, clavulanate and beta-lactams resulted in multiplicative reductions in their minimal inhibitory concentration (MIC) values. The MIC of amoxicillin against a panel of clinical isolates decreased more than 200-fold within this quadruple combination. Amoxicillin/clavulanate formulations are readily available with clinical pedigree, low toxicity, and orally and pediatric available; thus, supporting its potential inclusion as a new anti-BU drug in current combination therapies.

scholarly journals SENSITIVITY AND RESISTANCE TO ANTIMICROBIAL AGENTS ESBL-PRODUCING AND NOT PRODUCING ESBL STRAINS OF E. COLI IN PATIENTS WITH URINARY TRACT INFECTION

2019 ◽  
Vol 64 (2) ◽  
pp. 104-110
Author(s):  
N. I. Dimitrova ◽  
T. D. Gasretova ◽  
E. L. Alutina ◽  
G. G. Kharseeva
Keyword(s):  
Urinary Tract ◽  
Antimicrobial Agents ◽  
Beta Lactamase ◽  
Test Results ◽  
Beta Lactams ◽  
Esbl Production ◽  
E Coli ◽  
Amoxicillin Clavulanate ◽  
Resistant Strains ◽  
Tract Infections

As a result of the conducted researches it is shown that 44.1% of urinary tract infections (UTIS) caused by E. coli are accounted for by producers of beta-lactamase of the extended spectrum of action (ESBL). Associated resistance to fluoroquinolones and co-trimoxazole was found in 93.3% of BLRS-producing E. coli strains. All studied strains regardless of ESBL production were sensitive to imipenem, the majority showed sensitivity to ertapenem, gentamicin and resistance to doxycycline. Not producing ESBL strains of E. coli were sensitive to fosfomycin. Comparison of data obtained during testing of isolated cultures on ESBL, study of their sensitivity and resistance to beta-lactams (amoxicillin/clavulanate, ceftazidime, ceftriaxone, cefotaxime, imipenem) indicates the need to test isolates for AmpC products. To this end, during the screening test for ESBL and the method of «double disks», along with cephalosporins of III generation, it is necessary to use a phenotypic test for sensitivity to cefepime. The use of test results of E. coli isolates isolated from patients with UTIS for the production of ESBL, ampC enzymes, carbapenemase and sensitivity to AMP will improve the effectiveness of antimicrobial therapy and will help to curb the formation and spread of antimicrobial-resistant strains.

In vitro susceptibility of ceftolozane/tazobactam against typhoidal, non-typhoidal and extended spectrum β-lactamase-producing Salmonella

2021 ◽  
Author(s):  
Jade L. L. Teng ◽  
Elaine Chan ◽  
Asher C. H. Dai ◽  
Gillian Ng ◽  
Tsz Tuen Li ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Agents ◽  
The United States ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Extended Spectrum ◽  
Control And Prevention ◽  
Esbl Producers

Both typhoidal and non-typhoidal salmonellae are included in the top 15 drug-resistant threats described by the Center for Disease Control and Prevention of the United States. There is an urgent need to look for alternative antibiotics for the treatment of Salmonella infections. We examined the in vitro susceptibilities of ceftolozane/tazobactam and six other antibiotics on typhoidal and non-typhoidal salmonellae, including isolates that are extended-spectrum β-lactamase (ESBL)-positive, using the broth microdilution test. Of the 313 (52 typhoidal and 261 non-typhoidal) Salmonella isolates tested, 98.7% were susceptible to ceftolozane/tazobactam. Based on the overall MIC 50/90 values, Salmonella isolates were more susceptible to ceftolozane/tazobactam (0.25/0.5 mg/L) compared to all other comparator agents: ampicillin (≥64/≥64 mg/L), levofloxacin (0.25/1 mg/L), azithromycin (4/16 mg/L), ceftriaxone (≤0.25/4 mg/L), chloramphenicol (8/≥64 mg/L) and trimethoprim/sulfamethoxazole (1/≥8 mg/L). When comparing the activity of the antimicrobial agents against non-typhoidal Salmonella isolates according to their serogroup, ceftolozane/tazobactam had the highest activity (100%) against Salmonella serogroups D, G, I and Q isolates, whereas the lowest activity (85.7%) was observed against serogroup E isolates. All the 10 ESBL-producing Salmonella (all non-typhoidal) isolates, of which 8 were CTX-M-55-producers and 2 were CTX-M-65-producers, were sensitive to ceftolozane/tazobactam albeit with a higher MIC 50/90 value (1/2 mg/L) than non-ESBL-producers (0.25/0.5 mg/L). In summary, our data indicate that ceftolozane/tazobactam is active against most strains of both typhoidal and non-typhoidal salmonellae and also active against ESBL-producing salmonellae.

scholarly journals Antipneumococcal activities of cefpirome and cefotaxime, alone and in combination with vancomycin and teicoplanin, determined by checkerboard and time-kill methods.

1996 ◽  
Vol 40 (9) ◽  
pp. 1973-1976 ◽  
Author(s):  
S Bajaksouzian ◽  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Beta Lactams ◽  
Pneumococcal Infections ◽  
Titration Method ◽  
Resistant Strains ◽  
Time Kill ◽  
Checkerboard Titration

The checkerboard titration method was used to test the synergy of cefpirome and cefotaxime with teicoplanin or vancomycin against 35 penicillin-susceptible, 34 penicillin-intermediate, and 31 penicillin-resistant pneumococci. The MICs at which 50 and 90% of isolates are inhibited (MIC50s and MIC90s, respectively) of both cefpirome and cefotaxime were 0.016 and 0.06 microgram/ml, respectively, for penicillin-susceptible strains and 0.125 and 0.5 microgram/ml, respectively, for penicillin-intermediate strains. The MIC50s and MIC90s of cefotaxime for penicillin-resistant strains were 1.0 and 2.0 micrograms/ml, respectively, and those of cefpirome were 0.5 and 1.0 microgram/ml, respectively. All pneumococci were inhibited by cefpirome at MICs of < or = 1.0 microgram/ml. The MIC50s and MIC90s of vancomycin and teicoplanin (0.25 and 0.25 microgram/ml and 0.03 and 0.03 microgram/ml, respectively) did not differ for the three groups. Checkerboard synergy studies showed that cefpirome and vancomycin showed synergy for 31 strains (fractional inhibitory concentration [FIC] indices, < or = 0.5) cefpirome and teicoplanin showed synergy for 18 strains, cefotaxime and vancomycin showed synergy for 51 strains, and cefotaxime and teicoplanin showed synergy for 27 strains. Cefpirome and vancomycin had FIC indices indicating indifference (2.0) for two strains, and cefotaxime and vancomycin had FIC indices indicating indifference for one strain. All other FIC indices indicating indifference or additivity were > 0.5 to 1.0. No FIC indices indicating antagonism (> 4.0) were found. Synergy between beta-lactams and glycopeptides for three susceptible, three intermediate, and three resistant strains were tested by the time-kill assay, and all combinations were synergistic by this method. Synergy between cephalosporins and glycopeptides can be demonstrated and may be useful for the treatment of pneumococcal infections, especially meningitis.

scholarly journals Variation in erythromycin and clindamycin susceptibilities of Streptococcus pneumoniae by four test methods.

1997 ◽  
Vol 41 (1) ◽  
pp. 129-134 ◽  
Author(s):  
E L Fasola ◽  
S Bajaksouzian ◽  
P C Appelbaum ◽  
M R Jacobs
Keyword(s):  
Streptococcus Pneumoniae ◽  
Susceptibility Testing ◽  
Ambient Air ◽  
Test Methods ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Agar Dilution ◽  
Resistant Strains

Susceptibilities of 124 strains of Streptococcus pneumoniae to erythromycin and clindamycin were determined by the National Committee for the Clinical Laboratory Standards (NCCLS) broth microdilution method, with incubation for 20 to 24 h in ambient air and with modifications of this method by incubation for up to 48 h in air and CO2. Strains were also tested by agar dilution, E-test, and disk diffusion; good correlation was obtained with these methods, with clear separation into bimodal populations of susceptible and resistant stains. The broth microdilution method, however, using incubation in air for 24 h (NCCLS method), misclassified 4 of 92 erythromycin-resistant strains (1 as susceptible and 3 as intermediate) and 25 of 58 clindamycin-resistant strains (all as susceptible). With the exception of one strain with clindamycin, susceptible and resistant strains were correctly classified by the microdilution method with incubation in CO2 for 24 h or in ambient air for 48 h. Disk diffusion, agar dilution, and E-test methods with incubation in 5% CO2 are therefore reliable methods for susceptibility testing of pneumococci against these agents. However, the NCCLS microdilution method, which specifies incubation for 20 to 24 h in ambient air, produced significant very major errors (43%) clindamycin. Modification of the microdilution method by incubation in 5% CO2 or by extension of incubation time in ambient air to 48 h corrected these errors. Disk diffusion, however, was shown to be a simple, convenient, and reliable method for susceptibility testing of pneumococci to erythromycin and clindamycin and is suggested as the method of choice for these agents.

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