Comparative Pharmacodynamics of Three Newer Fluoroquinolones versus Six Strains of Staphylococci in an In Vitro Model under Aerobic and Anaerobic Conditions

Wright, David H.; Gunderson, Brent W.; Hovde, Laurie B.; Ross, Gigi H.; Ibrahim, Khalid H.; Rotschafer, John C.

doi:10.1128/aac.46.5.1561-1563.2002

Cited by 18 publications

(15 citation statements)

References 10 publications

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“…Overall, only 30 to 50% of the observations in these studies provided useful information. It is fair to say that similar problems also were inherent in more rigorously designed dose (AUC/MIC)-ranging studies (17,18,25,27,33). For example, in studies where S. pneumoniae (17), B. fragilis (25), and Bacteroides thetaiotamicron (27) were exposed to wide ranges of quinolone AUC 24 /MIC values, quantitative data could be obtained in only 10 to 66% of experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Agents Chemother., poster A-440, 2001). Despite wide ranges of AUC/MIC ratios simulated in some recent studies (17)(18)(19)(20)27,33; MacGowan and Bowker, 41st ICAAC), reasonable relationships with resistance were not established. The relatively few studies of these relationships can be classified as those that directly attempt to relate resistance to the simulated pharmacokinetics but do not (17,20) and those that imply the existence of relationships with the AUC/MIC ratio measured within a 24-h dosing interval (AUC 24 /MIC) or with the C max /MIC ratio but do not actually report them (26,27,30).…”

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confidence: 99%

“…Limited observations reported from earlier timekill studies (3, 8, 21-23) precluded delineation of relationships of the area under the concentration-time curve (AUC)/MIC ratio with resistance because the ranges of the simulated AUCto-MIC ratios were too narrow. In fact, the first attempts to relate resistance to the AUC/MIC or peak concentration (C max )/MIC ratio were reported quite recently from studies that declared resistance analysis as a primary goal (1,7,17,18,20,(25)(26)(27)30,33,34; A. MacGowan and K. Bowker, Abstr. 41st Intersci.…”

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confidence: 99%

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In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus

Firsov

Vostrov

Lubenko

et al. 2003

Antimicrob Agents Chemother

201

183

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Examination of time-kill curves of antibiotic-exposed bacteria using in vitro dynamic models allows pharmacokinetically related comparisons of antimicrobial effects but may or may not directly reflect the selective enrichment of resistant mutants. Bacterial resistance has been studied infrequently using these models. Limited observations reported from earlier timekill studies (3, 8, 21-23) precluded delineation of relationships of the area under the concentration-time curve (AUC)/MIC ratio with resistance because the ranges of the simulated AUCto-MIC ratios were too narrow. In fact, the first attempts to relate resistance to the AUC/MIC or peak concentration (C max )/MIC ratio were reported quite recently from studies that declared resistance analysis as a primary goal (1,7,17,18,20,(25)(26)(27)30,33,34; A. MacGowan and K. Bowker, Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., poster A-440, 2001). Despite wide ranges of AUC/MIC ratios simulated in some recent studies (17)(18)(19)(20)27,33; MacGowan and Bowker, 41st ICAAC), reasonable relationships with resistance were not established. The relatively few studies of these relationships can be classified as those that directly attempt to relate resistance to the simulated pharmacokinetics but do not (17,20) and those that imply the existence of relationships with the AUC/MIC ratio measured within a 24-h dosing interval (AUC 24 /MIC) or with the C max /MIC ratio but do not actually report them (26,27,30). One study did report a complex effect of AUC 24 /MIC and duration of moxifloxacin treatment on bacterial resistance (MacGowan and Bowker, 41st ICAAC), but the three-dimensional plots masked rather than highlighted these links. For example, according to an analysis of these data (A. Firsov, S. Vostrov, I. Lubenko, S. Zinner, and Y. Portnoy, Abstr. 42nd Intersci. Conf. Antimicrob. Agents Chemother., abstr. A-1210Chemother., abstr. A- , p. 10, 2002, the reported 72-h area under the population analysis profile-time curve as an index of pneumococcal resistance did not correlate with simulated AUC 24 /MIC ratios (r 2 , 0.04).

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus

Firsov

Vostrov

Lubenko

et al. 2003

Antimicrob Agents Chemother

201

183

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“…Gli studi effettuati con modelli in vitro hanno dimostrato che la moxifloxacina è dotata di un elevato potere battericida nei confronti dei ceppi sensibili [65][66][67][68][69][70][71][72][73][74] .…”

Section: Farmacodinamicaunclassified

Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomico

Eandi

2003

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PREMESSEMoxifloxacina è un nuovo fluorochinolone di recente introduzione nell'armamentario terapeutico per il trattamento antibiotico delle infezioni delle basse ed alte vie respiratorie [1][2][3][4][5][6][7].Moxifloxacina è un 8-metossichinolone dotato di un ampio spettro d'azione antibatterico nei confronti dei batteri Grampositivi e Gram-negativi, aerobi ed anaerobi e dei patogeni atipici quali micoplasmi, legionelle e clamidie [3, 7, 8]. Questo nuovo antibiotico è tra i farmaci più potenti attualmente disponibili nei confronti dei batteri Gram-positivi, compresi lo Staphylococcus aureus meticillino-resistente e i pneumococchi, sia sensibili che resistenti alla penicillina. La moxifloxacina è attiva quanto la ciprofloxacina verso Legionella spp., ma più attiva verso Chlamydia spp. e Mycoplasma pneumoniae. Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomicoMario Eandi * Moxifloxacina manifesta minore efficacia rispetto a ciprofloxacina verso le Enterobatteriaceae e verso Pseudomonas aeruginosa. Dotata di una potente e rapida azione battericida concentrazione-dipendente verso i batteri Gram-positivi e di un marcato effetto post-antibiotico, la moxifloxacina si accumula rapidamente nei ceppi sensibili, agisce inibendo in ugual misura sia la DNA girasi sia la topoisomerasi IV e manifesta una ridotta tendenza a selezionare ceppi mutanti resistenti [1, 7].La farmacocinetica della moxifloxacina si caratterizza per la lunga emivita, circa 12 ore, per un'elevata biodisponibilità orale, un'eccellente diffusibilità tissutale extravascolare e per la scarsità di interazioni con altri farmaci [1, 7]. Il profilo di tollerabilità, simile a quello dei fluorochinoloni, si differenzia, tuttavia, per l'assenza di fototossicità [2]. ABSTRACTMoxifloxacin is a new fluorquinolone antibiotic, recently introduced among the treatment options for upper and lower airways infections. It possesses a wide antibiotic spectrum, covering the major pathogens involved in the genesis of community acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and acute bacterial sinusitis (ABS). It acts in a concentration-dependent manner by inhibition of bacterial DNAgirase and topoisomerase IV, has a long biological half-life (about 12 hours), good oral bioavailability, excellent tissue diffusion and a better safety profile than other quinolones, because of the lack of phototoxicity and the scarsity of clinically significant drug interactions. The clinical results of moxifloxacin in CAP, AECB and ABS have been compared with those of available alternative antibiotics in several multicentric, double-blind studies, and the new fluorquinolone resulted at least as effective as the comparators, with similar tolerability profiles. These studies demonstrated a high correlation among the eradication of the pathogen and the clinical recovery of the patients. The pharmacodynamics, pharmacokinetics and clinical results of moxifloxacin render it one of the most attractive options for the empirical treatment of upper and lower air...

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“…The maximum antibacterial effects and the AUC/MIC ratios for various effects were similar in aerobic and anaerobic conditions. This builds on the earlier work of Wright et al (24), who showed that levofloxacin, trovafloxacin, and moxifloxacin were rapidly bactericidal against staphylococci in an in vitro model, irrespective of aerobic or anaerobic growth conditions.…”

Section: Micsmentioning

confidence: 99%

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

Noel

Bowker

MacGowan

2005

Antimicrob Agents Chemother

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The antibacterial effects of moxifloxacin against Bacteroides fragilis, Clostridium perfringens, and grampositive 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 maximumeffect 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.In vitro pharmacokinetic models have been widely used to establish and justify fluoroquinolone-dosing strategies against aerobic gram-positive and gram-negative bacteria. Indeed, fluoroquinolones are probably the most studied antibiotic class in terms of pharmacodynamics, with strong links established between observations in in vitro and animal pharmacodynamic systems and subsequent observations in humans (19,20,22). It can be argued that the present pharmacodynamic paradigm, in terms of optimizing therapeutic outcomes while minimizing the risk of antibiotic resistance, has been developed largely using data on fluoroquinolones (6).In contrast to the situation with aerobic bacteria, the pharmacodynamics of fluoroquinolones against anaerobic species is very poorly studied; however, it is clear that the in vitro potencies of newer agents, such as clinafloxacin, moxifloxacin, sitafloxacin, and trovafloxacin, are good and include potencies against Bacteroides spp. (4). In addition, animal model data for some agents have been encouraging (3), as have the results of clinical trials against standard therapies (5, 18, 21, 23). Data using in vitro ph...

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Comparative Pharmacodynamics of Three Newer Fluoroquinolones versus Six Strains of Staphylococci in an In Vitro Model under Aerobic and Anaerobic Conditions

Cited by 18 publications

References 10 publications

In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus

In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus

Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomico

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

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