scholarly journals Twenty-four-hour area under the concentration-time curve/MIC ratio as a generic predictor of fluoroquinolone antimicrobial effect by using three strains of Pseudomonas aeruginosa and an in vitro pharmacodynamic model.

1996 ◽  
Vol 40 (3) ◽  
pp. 627-632 ◽  
Author(s):  
K J Madaras-Kelly ◽  
B E Ostergaard ◽  
L B Hovde ◽  
J C Rotschafer
Keyword(s):  
Antibacterial Effect ◽  
Antimicrobial Effect ◽  
Time Curve ◽  
Emax Model ◽  
Concentration Time ◽  
Mueller Hinton ◽  
Kill Curve ◽  
Time Kill ◽  
Mueller Hinton Broth

Several investigators have suggested that the 24-h area under the concentration-time curve (AUC)/MIC ratio (AUC/MIC24 or AUIC24) can be used to make comparisons of antimicrobial activity between fluoroquinolone antibiotics. Limited data exist regarding the generic predictive ability of AUC/MIC24 for the antimicrobial effects of fluoroquinolones. The purposes of the present investigation were to determine if the AUC/MIC24 can be used as a generic outcome predictor of fluoroquinolone antibacterial activity and to determine if a similar AUC/MIC24 breakpoint can be established for different fluoroquinolones. Using an in vitro pharmacodynamic model, 29 duplicate concentration time-kill curve experiments simulated AUC/MIC24s ranging from 52 to 508 SIT-1.h (inverse serum inhibitory titer integrated over time) with ciprofloxacin or ofloxacin against three strains of Pseudomonas aeruginosa. Each 24-h experiment was performed in cation-supplemented Mueller-Hinton broth with a starting inoculum of 10(6) CFU/ml. At timed intervals cation-supplemented Mueller-Hinton broth samples were collected for CFU and fluoroquinolone concentration determinations. Transformation of bacterial counts into the cumulative bacterial effect parameter of the 24-h area under the effect curve (AUEC24) was performed for each concentration time-kill curve. Multivariate regression analysis was used to compare pharmacodynamic predictors (AUC/MIC24, 24-h AUC, peak concentration [Cmax] to MIC ratios [Cmax:MIC], etc.) with ln AUEC24. To identify threshold breakpoint AUC/MIC24s, AUEC24s were stratified by the magnitude of AUC/MIC24 into subgroups, which were analyzed for differences in antibacterial effect. The Kruskal-Wallis test and subsequent Tukey's multiple comparison test were used to determine which AUC/MIC subgroups were significantly different. Multiple regression analysis revealed that only AUC/MIC24 (r2 = 0.65) and MIC (r2 = 0.03) were significantly correlated with antibacterial effect. At similar AUC/MIC24s, yet different MICs, Cmaxs, or elimination half-lives, the AUEC24s were similar for both fluoroquinolones. The relationship between AUC/MIC24 and ln AUEC24 was best described by a sigmoidal maximal antimicrobial effect (Emax) model (r2 = 0.72; Emax = 9.1; AUC/MIC50 = 119 SIT-1.h; S = 2.01 [S is an exponent that reflects the degree of sigmoidicity]). Ciprofloxacin-bacteria AUC/MIC24 values of < 100 SIT-1.h were significantly different (P < 0.05) from the AUC/MIC24 values of > 100 SIT-1.h. An ofloxacin AUC/MIC24 of > 100 SIT-1.h and an AUC/MIC24 of < 100 SIT-1.h exhibited a trend toward a significant difference (P > 0.05 but < 0.1). The inverse relationship between drug exposure and MIC increase postexposure was described by a sigmoidal fixed Emax model (AUC/MIC24, r2 = 0.40; AUC/MIC50 = 95 SIT-1.h; S = 1.97; Cmax:MIC, r2 = 0.41; Cmax:MIC50 = 7.3; S = 2.01). These data suggest that AUC/MIC24 may be the most descriptive measurement of fluoroquinolone antimicrobial activity against P. aeruginosa, that ofloxacin and ciprofloxacin have similar AUC/MIC24 threshold breakpoints at approximately 100 SIT-1.h, that the concentration-dependent selection of resistant organisms may parallel the threshold breakpoint of the antimicrobial effect, and that AUC/MIC24 generically describes the antibacterial effects of different fluoroquinolones.

scholarly journals Relationships of the Area under the Curve/MIC Ratio to Different Integral Endpoints of the Antimicrobial Effect: Gemifloxacin Pharmacodynamics in an In Vitro Dynamic Model

2001 ◽  
Vol 45 (3) ◽  
pp. 927-931 ◽  
Author(s):  
Alexander A. Firsov ◽  
Irene Y. Lubenko ◽  
Yury A. Portnoy ◽  
Stephen H. Zinner ◽  
Sergey N. Vostrov
Keyword(s):  
Area Under The Curve ◽  
Antimicrobial Effect ◽  
Time Curve ◽  
Marginal Value ◽  
Actual Effect ◽  
Control Growth ◽  
Effect Duration ◽  
Kill Curve ◽  
Time Kill

ABSTRACT Most integral endpoints of the antimicrobial effect are determined over an arbitrarily chosen time period, such as the dosing interval (τ), regardless of the actual effect duration. Unlike the τ-related endpoints, the intensity of the antimicrobial effect (I E) does consider its duration—from time zero to the time when bacterial counts on the regrowth curve achieve the same maximal numbers as in the absence of the antimicrobial. To examine the possible impact of this fundamental difference on the relationships of the antimicrobial effect to the ratio of the area under the concentration-time curve (AUC) to the MIC, a clinical isolate ofStaphylococcus aureus was exposed to simulated gemifloxacin pharmacokinetics over a 40-fold range of AUC/MIC ratios, from 11 to 466 h. In each run, I E and four τ-related endpoints, including the area under the time-kill curve (AUBC), the area above the curve (AAC), the area between the control growth and time-kill curves (ABBC), and the ABBC related to the area under the control growth curve (AUGC), were calculated for τ = 24 h. Unlike the I E, which displayed pseudolinear relationships with the AUC/MIC ratio; each τ-related endpoint showed a distinct saturation at potentially therapeutic AUC/MIC ratios (116 to 466 h) when the antimicrobial effect persisted longer than τ. This saturation results from the underestimation of the true effect and may be eliminated if ABBC, AAC, and AUBC (but not AUGC) are modified and determined in the same manner as the I E to consider the actual effect duration. These data suggest a marginal value of the τ-related endpoints as indices of the total antimicrobial effect. Since all of them respond to AUC/MIC ratio changes less than theI E, the latter is preferable in comparative pharmacodynamic studies.

scholarly journals In vitro Antimicrobial Potency of Lemon Fruit (Citrus limon) Extract on Salmonella typhi

2020 ◽  
Vol 11 (2) ◽  
pp. 69
Author(s):  
Farhan Haidar Fazlur Rahman ◽  
Lindawati Alimsardjono ◽  
Sunarni Zakaria
Keyword(s):  
Agar Plate ◽  
Antimicrobial Effect ◽  
Salmonella Typhi ◽  
Citrus Limon ◽  
Lemon Fruit ◽  
Mueller Hinton ◽  
Antibacterial Spectrum ◽  
Mueller Hinton Broth

Introduction: This study aimed to evaluate minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of lemon fruit (Citrus limon) extract in inhibiting Salmonella typhi growth in vitro.Methods: This research was categorized as a laboratory experimental study. Lemon fruit (Citrus limon) extract was prepared with concentration as follows: 100.000 ppm, 50.000 ppm, 25.000 ppm, 12.500 ppm, 6.250 ppm, 3.125 ppm, 1.562 ppm, 781 ppm, and 390 ppm. Dilution tests with Mueller-Hinton broth medium were performed to determine the MIC. After 24 hours of incubation, isolated Salmonella typhi inside the tube was inoculated back in MacConkey agar plate medium to determine the MBC. Replications were conducted 3 times according to Federer’s formula.Results: MIC of lemon fruit (Citrus limon) extract to Salmonella typhi was determined at 3.125 ppm. Meanwhile, MBC was determined at 6.250 ppm.Conclusion: This study showed the potential antimicrobial effect of lemon fruit (Citrus limon) extract against Salmonella typhi in-vitro. Further studies are still needed to determine its efficacy and safety in vivo and also its full antibacterial spectrum. 

scholarly journals MIC-Based Interspecies Prediction of the Antimicrobial Effects of Ciprofloxacin on Bacteria of Different Susceptibilities in an In Vitro Dynamic Model

1998 ◽  
Vol 42 (11) ◽  
pp. 2848-2852 ◽  
Author(s):  
Alexander A. Firsov ◽  
Sergey N. Vostrov ◽  
Alexander A. Shevchenko ◽  
Stephen H. Zinner ◽  
Giuseppe Cornaglia ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Bacterial Species ◽  
Maximal Effect ◽  
Bacterial Strains ◽  
Time Curve ◽  
Antimicrobial Effects ◽  
E Coli ◽  
Kill Curve ◽  
Time Kill

ABSTRACT Multiple predictors of fluoroquinolone antimicrobial effects (AMEs) are not usually examined simultaneously in most studies. To compare the predictive potentials of the area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC), the AUC above MIC (AUCeff), and the time above MIC (T eff), the kinetics of killing and regrowth of four bacterial strains exposed to monoexponentially decreasing concentrations of ciprofloxacin were studied in an in vitro dynamic model. The MICs of ciprofloxacin for clinical isolates ofStaphylococcus aureus, Escherichia coli11775 (I) and 204 (II), and Pseudomonas aeruginosa were 0.6, 0.013, 0.08, and 0.15 μg/ml, respectively. The simulated values of AUC were designed to provide similar 1,000-fold (S. aureus, E. coli I, and P. aeruginosa) or 2,000-fold (E. coli II) ranges of the AUC/MIC. In each case except for the highest AUC/MIC ratio, the observation periods included complete regrowth in the time-kill curve studies. The AME was expressed by its intensity,I E (the area between the control growth and time-kill and regrowth curves up to the point where the viable counts of regrowing bacteria are close to the maximum values observed without drug). For most AUC ranges the I E-AUC curves were fitted by an E max (maximal effect) model, whereas the effects observed at very high AUCs were greater than those predicted by the model. The AUCs that produced 50% of maximal AME were proportional to the MICs for the strains studied, but maximal AMEs (I E max ) and the extent of sigmoidicity (s) were not related to the MIC. BothT eff and log AUC/MIC correlated well withI E (r 2 = 0.98 in both cases) in a species-independent fashion. UnlikeT eff or log AUC/MIC, a specific relationship between I E and log AUCeff was inherent in each strain. Although each I E and log AUCeff plot was fitted by linear regression (r 2 = 0.97 to 0.99), these plots were not superimposed and therefore are bacterial species dependent. Thus, AUC/MIC and T eff were better predictors of ciprofloxacin’s AME than AUCeff. This study suggests that optimal predictors of the AME produced by a given quinolone (intraquinolone predictors) may be established by examining its AMEs against bacteria of different susceptibilities.T eff was shown previously also to be the best interquinolone predictor, but unlike AUC/MIC, it cannot be used to compare different quinolones. AUC/MIC might be the best predictor of the AME in comparisons of different quinolones.

scholarly journals Antistaphylococcal Effect Related to the Area under the Curve/MIC Ratio in an In Vitro Dynamic Model: Predicted Breakpoints versus Clinically Achievable Values for Seven Fluoroquinolones

2005 ◽  
Vol 49 (7) ◽  
pp. 2642-2647 ◽  
Author(s):  
Alexander A. Firsov ◽  
Irene Y. Lubenko ◽  
Sergey N. Vostrov ◽  
Yury A. Portnoy ◽  
Stephen H. Zinner
Keyword(s):  
In Vitro Model ◽  
Therapeutic Potential ◽  
Area Under The Curve ◽  
Antimicrobial Effect ◽  
Clinical Isolates ◽  
Clinical Settings ◽  
Time Curve ◽  
Concentration Time ◽  
Vitro Model

ABSTRACT Prediction of the relative efficacies of different fluoroquinolones is often based on the ratios of the clinically achievable area under the concentration-time curve (AUC) to the MIC, usually with incorporation of the MIC50 or the MIC90 and with the assumption of antibiotic-independent patterns of the AUC/MIC-response relationships. To ascertain whether this assumption is correct, the pharmacodynamics of seven pharmacokinetically different quinolones against two clinical isolates of Staphylococcus aureus were studied by using an in vitro model. Two differentially susceptible clinical isolates of S. aureus were exposed to two 12-h doses of ciprofloxacin (CIP) and one dose of gatifloxacin (GAT), gemifloxacin (GEM), grepafloxacin (GRX), levofloxacin (LVX), moxifloxacin (MXF), and trovafloxacin (TVA) over similar AUC/MIC ranges from 58 to 932 h. A specific bacterial strain-independent AUC/MIC relationship with the antimicrobial effect (IE ) was associated with each quinolone. Based on the IE -log AUC/MIC relationships, breakpoints (BPs) that are equivalent to a CIP AUC/MIC ratio of 125 h were predicted for GRX, MXF, and TVA (75 to 78 h), GAT and GEM (95 to 103 h) and LVX (115 h). With GRX and LVX, the predicted BPs were close to those established in clinical settings (no clinical data on other quinolones are available in the literature). To determine if the predicted AUC/MIC BPs are achievable at clinical doses, i.e., at the therapeutic AUCs (AUCthers), the AUCther/MIC50 ratios were studied. These ratios exceeded the BPs for GAT, GEM, GRX, MXF, TVA, and LVX (750 mg) but not for CIP and LVX (500 mg). AUC/MIC ratios above the BPs can be considered of therapeutic potential for the quinolones. The highest ratios of AUCther/MIC50 to BP were achieved with TVA, MXF, and GEM (2.5 to 3.0); intermediate ratios (1.5 to 1.6) were achieved with GAT and GRX; and minimal ratios (0.3 to 1.2) were achieved with CIP and LVX.

scholarly journals Pharmacodynamics of Moxifloxacin against Anaerobes Studied in an In Vitro Pharmacokinetic Model

2005 ◽  
Vol 49 (10) ◽  
pp. 4234-4239 ◽  
Author(s):  
Alan R. Noel ◽  
Karen E. Bowker ◽  
Alasdair P. MacGowan
Keyword(s):  
Pharmacokinetic Model ◽  
Antibacterial Effect ◽  
Maximum Effect ◽  
Wild Type ◽  
Time Curve ◽  
Concentration Time ◽  
Effect Measure ◽  
Dose Ranging ◽  
Emergence Of Resistance

ABSTRACT The antibacterial effects of moxifloxacin against Bacteroides fragilis, Clostridium perfringens, and gram-positive anaerobic cocci (GPAC) were studied in an in vitro pharmacokinetic model. Initially, a dose-ranging study with area under the concentration-time curve (AUC)/MIC ratios of 6.7 to 890 was used to investigate the effect of anaerobic conditions on the AUC/MIC antibacterial effect (ABE) relationship with Escherichia coli. The AUC/MIC ratios for 50% and 90% effects, using a log CFU drop at 24 h as the antibacterial effect measure, were 34 and 59, respectively, aerobic and 54 and 96, respectively, anaerobic. These values are not significantly different. Dose ranging at AUC/MIC ratios of 9 to 216 against the anaerobes indicated a differing AUC/MIC ABE pattern, and the AUC/MICs for 50% and 90% effects were lower: for B. fragilis, they were 10.5 and 25.7, respectively; for C. perfringens, they were 8.6 and 16.2; and for GPAC, they were 7.3 and 17.4. The maximum-effect log drops were as follows: for B. fragilis, −3.2 ± 0.2 logs; for C. perfringens, −3.7 ± 0.1 logs; and for GPAC, −2.5 ± 0.1 logs. Although the anaerobes were not eradicated, there was no emergence of resistance. Comparison of the ABE of moxifloxacin to that of ertapenem against B. fragilis indicated that moxifloxacin was superior at 24 h and 48 h. In contrast, ertapenem was superior to moxifloxacin against GPAC at 24 h and 48 h and against C. perfringens at 48 h. Both drugs performed equivalently against C. perfringens at 24 h. Monte Carlo simulations using human serum AUC data and an AUC/MIC anaerobe target of 7.5 suggests a >90% target achievement at MICs of <2 mg/liter. This divides the B. fragilis wild-type MIC distribution. The pharmacodynamic properties of moxifloxacin against anaerobes are different than those against aerobic species. The clinical implications of these differences need further exploration.

scholarly journals Comparative in vitro pharmacodynamics of imipenem and meropenem against Pseudomonas aeruginosa.

1996 ◽  
Vol 40 (4) ◽  
pp. 904-908 ◽  
Author(s):  
R White ◽  
L Friedrich ◽  
D Burgess ◽  
D Warkentin ◽  
J Bosso
Keyword(s):  
Drug Exposure ◽  
Antimicrobial Agents ◽  
Testing Procedure ◽  
Rank Test ◽  
Time Curve ◽  
Bacterial Killing ◽  
Drug Degradation ◽  
Concentration Time ◽  
Time Kill

MICs are commonly used to assess the in vitro activities of antimicrobial agents; however, they provide minimal information on the pattern of bacterial activities. Time-kill studies with extensive sampling allow assessment of both the rate and extent of bacterial killing and regrowth. We compared imipenem and meropenem by both MIC-MBC testing and a time-kill study with P. aeruginosa 27853. In the time-kill study, concentration/MIC ratios ranging from 0.0625 to 32 times the MIC were studied. The kill rate, time to 99.9% kill, doubling time of regrowth, and area under the bacterial killing curve (AUKC) were evaluated. Degradation during the testing procedure was accounted for by assessing actual drug exposure as determined by the area under the concentration-time curve. Pharmacodynamic parameters were compared by using the Wilcoxon signed-rank test. The modal MIC and MBC for imipenem were 2 and 4 micrograms/ml, respectively, and those for meropenem were 0.25 and 0.5 microgram/ml, respectively. In the time-kill study, both agents displayed concentration-dependent activity over a range of 0.25 to 4 times the MIC. Initial killing (0 to 1 h) was faster with imipenem at the same concentration/MIC ratios (P = 0.0506). The time to 99.9% kill was approximately 5 h for both agents. When regrowth occurred, the doubling rate for imipenem, which was the same as that for the growth control, was twice as rapid as that for meropenem. At the same concentrations, the AUKCs over 24 h were lower for meropenem than for imipenem (P = 0.0280); however, when normalized by MIC, imipenem resulted in smaller AUKCs. Comparison of plots of area under the concentration-time curve versus AUKC, which accounted for drug degradation and actual drug exposure, revealed that meropenem was three times more active than imipenem, rather than the eightfold difference suggested by MICs. Time-kill curves with extensive sampling and measurement of actual drug exposure, rather than traditional MIC testing, may more accurately assess differences in the in vitro activities of antimicrobial agents.

scholarly journals Pharmacokinetic and Pharmacodynamic Parameters for Antimicrobial Effects of Cefotaxime and Amoxicillin in an In Vitro Kinetic Model

2001 ◽  
Vol 45 (9) ◽  
pp. 2436-2440 ◽  
Author(s):  
I. Gustafsson ◽  
E. Löwdin ◽  
I. Odenholt ◽  
O. Cars
Keyword(s):  
Kinetic Model ◽  
Streptococcus Pyogenes ◽  
Elimination Rate ◽  
Antimicrobial Effect ◽  
Drug Elimination ◽  
Time Curve ◽  
Initial Concentration ◽  
E Coli ◽  
Concentration Time

ABSTRACT An in vitro kinetic model was used to study the relation between pharmacokinetic and pharmacodynamic (PK-PD) parameters for antimicrobial effect, e.g., the time above MIC (T>MIC), maximum concentration in serum (C max), and area under the concentration-time curve (AUC). Streptococcus pyogenes and Escherichia coli were exposed to cefotaxime, and the activity of amoxicillin against four strains ofStreptococcus pneumoniae with different susceptibilities to penicillin was studied. The drug elimination rate varied so that the T>MIC ranged from 20 to 100% during 24 h, while the AUC and/or the initial concentration (C max) were kept constant. For S. pyogenes and E. coli, the maximal antimicrobial effect (E max) at 24 h occurred when the antimicrobial concentration exceeded the MIC for 50 and 80% of the strains tested, respectively. The penicillin-susceptible pneumococci (MIC, 0.03 mg/liter) and the penicillin-intermediate strain (MIC, 0.25 mg/liter) showed maximal killing by amoxicillin at a T>MIC of 50%. For a strain for which the MIC was 2 mg/liter, C max needed to be increased to achieve the E max. Under the condition that C max was 10 times the MIC,E max was obtained at a T>MIC of 60%, indicating that C max, in addition to T>MIC, may be an important parameter for antimicrobial effect on moderately penicillin-resistant pneumococci. For the strain for which the MIC was 4 mg/liter, the reduction of bacteria varied from −0.4 to −3.6 log10 CFU/ml at a T>MIC of 100%, despite an initial antimicrobial concentration of 10 times the MIC. Our studies have shown that the in vitro kinetic model is a useful complement to animal models for studying the PK-PD relationship for antimicrobial effect of antibiotics.

scholarly journals Inter- and Intraquinolone Predictors of Antimicrobial Effect in an In Vitro Dynamic Model: New Insight into a Widely Used Concept

1998 ◽  
Vol 42 (3) ◽  
pp. 659-665 ◽  
Author(s):  
Alexander A. Firsov ◽  
Alexander A. Shevchenko ◽  
Sergey N. Vostrov ◽  
Stephen H. Zinner
Keyword(s):  
Dynamic Model ◽  
Half Life ◽  
Antimicrobial Effect ◽  
Data Sets ◽  
Time Curve ◽  
Linear Relationships ◽  
Control Growth ◽  
Dosing Regimens ◽  
Time Kill

ABSTRACT Earlier efforts to search for pharmacokinetic and bacteriological predictors of fluoroquinolone antimicrobial effects (AMEs) have resulted in conflicting findings. To elucidate whether these conflicts are real or apparent, several predictors of the AMEs of two pharmacokinetically different antibiotics, trovafloxacin (TRO) and ciprofloxacin (CIP), as well as different dosing regimens of CIP were examined. The AMEs of TRO given once daily (q.d.) and CIP given q.d. and twice daily (b.i.d.) against Escherichia coli,Pseudomonas aeruginosa, and Klebsiella pneumoniae were studied in an in vitro dynamic model. Different monoexponential pharmacokinetic profiles were simulated with a TRO half-life of 9.2 h and a CIP half-life of 4.0 h to provide similar eightfold ranges of the area under the concentration-time curve (AUC)-to-MIC ratios, from 54 to 432 and from 59 to 473 (μg · h/ml)/(μg/ml), respectively. In each case the observation periods were designed to incorporate full-term regrowth phases in the time-kill curves, and the AME was expressed by its intensity (IE ; the area between the control growth and time-kill and regrowth curves up to the point at which the viable counts of regrowing bacteria are close to the maximum values observed without drug). Species-independent linear relationships were established between IE and log AUC/MIC, log AUC above MIC (log AUCeff), and time above the MIC (T eff). Specific and nonsuperimposedIE versus log AUC/MIC or log AUCeffrelationships were inherent in each of the treatments: TRO given q.d. (r 2 = 0.97 and 0.96), CIP given q.d. (r 2 = 0.98 and 0.96), and CIP given b.i.d. (r 2 = 0.95 and 0.93). This suggests that in order to combine data sets obtained with individual quinolones to examine potential predictors, one must be sure that these sets may be combined. Unlike AUC/MIC and AUCeff, the IE -T effrelationships plotted for the different quinolones and dosing regimens were nonspecific and virtually superimposed (r 2 = 0.95). Hence, AUC/MIC, AUCeff, and T eff were equally good predictors of the AME of each of the quinolones and each dosing regimen taken separately, whereas T eff was also a good predictor of the AMEs of the quinolones and their regimens taken together. However, neither the quinolones nor the dosing regimens could be distinguished solely on the basis of T eff, whereas they could be distinguished on the basis of AUC/MIC or AUCeff. Thus, two types of predictors of the quinolone AME may be identified: intraquinolone and/or intraregimen predictors (AUC/MIC, AUCeff and Teff) and an interquinolone and interregimen predictor (T eff). T eff may be able to accurately predict the AME of one quinolone on the basis of the data obtained for another quinolone.

scholarly journals In Vitro Bactericidal Activities of ABT-773 against ermB Strains of Streptococcus pneumoniae

2003 ◽  
Vol 47 (3) ◽  
pp. 1132-1134 ◽  
Author(s):  
Melinda M. Neuhauser ◽  
Jennifer L. Prause ◽  
Larry H. Danziger ◽  
Susan L. Pendland
Keyword(s):  
Streptococcus Pneumoniae ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Mueller Hinton ◽  
Amoxicillin Clavulanate ◽  
Horse Blood ◽  
Bactericidal Activities ◽  
Time Kill ◽  
Mueller Hinton Broth

ABSTRACT The bactericidal activities of ABT-773, a new ketolide, were compared to those of cefuroxime and amoxicillin-clavulanate against 10 strains of Streptococcus pneumoniae containing the ermB gene. MICs and time-kill curves were determined in duplicate per NCCLS guidelines with cation-adjusted Mueller-Hinton broth with 3% lysed horse blood. Viable counts were done at 0, 2, 6, and 24 h. Antibiotic concentrations tested were two and eight times the MIC. ABT-773 MICs ranged from 0.008 to 1.0 μg/ml. Bactericidal activity was observed with ABT-773 at eight times the MIC against 4 of 10 strains at 24 h compared to 10 of 10 strains with the beta-lactam antibiotics.

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