Benchmarking the in vitro activity of moxifloxacin against recent isolates of Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. A European multi-centre study

Jones, Mark; Staples, Angela M.; Critchley, Ian A.; Thornsberry, Clyde; Heinze, Paul; Engler, Howard D.; Sahm, Daniel F.

doi:10.1016/s0732-8893(00)00128-0

Cited by 22 publications

(17 citation statements)

References 28 publications

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“…54, p. 141, 1999). However, in this U.S.-wide study, similar to a recent European study (20), no isolates of either species required MICs of any of the fluoroquinolones tested of Ͼ1.0 g/ml, MIC 90 s for moxifloxacin were 0.03 g/ml for H. influenzae and 0.06 g/ml for M. catarrhalis, and there was no association with ␤-lactamase status for either species.…”

Section: Discussionsupporting

confidence: 73%

“…The incidence of ␤-lactamase production in both species remained mostly constant, irrespective of geographical location within the United States (MRL, unpublished data). This is in contrast to the situation in Europe and Asia, in which far greater regional differences have been reported (13,20,35). This is especially true for H. influenzae, which in some regional populations produces ␤-lactamase at an incidence of less than 5% (13,35).…”

Section: Discussionmentioning

confidence: 62%

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Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

Jones

Staples²,

Critchley³

et al. 2000

Antimicrob Agents Chemother

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To benchmark the activity of moxifloxacin (a newer fluoroquinolone), a U.S. study comprising 16,141 contemporary isolates of Streptococcus pneumoniae (5,640), Haemophilus influenzae (6,583), and Moraxella catarrhalis (3,648) referred from 377 institutions during 1998 is described. For S. pneumoniae the modal MIC and MIC at which 90% of the isolates were inhibited (MIC 90 ) for moxifloxacin were 0.12 and 0.25 g/ml, respectively, independent of susceptibility to other drug classes, geography, or site of infection. Eleven isolates were intermediate or resistant to levofloxacin and grepafloxacin; of these isolates, 1 remained susceptible to sparfloxacin, 2 remained susceptible to moxifloxacin, and 4 remained susceptible to trovafloxacin. All 11 isolates possessed classic mutations in gyrA and/or parC known to confer reduced susceptibility to fluoroquinolones. Four isolates (originating from four separate states) belonging to a multidrug-resistant, fluoroquinolone-resistant clone were identified by pulsed-field gel electrophoresis. For moxifloxacin and trovafloxacin, at least 87% of isolates demonstrated MICs >3 twofold concentrations below the susceptibility breakpoints, in contrast to no more than 15% for levofloxacin, grepafloxacin, and sparfloxacin. Of the isolates that were multidrug resistant (7.4%), >98% remained susceptible to moxifloxacin. The modal MIC and MIC 90 for M. catarrhalis (both 0.06 g/ml) and for H. influenzae (both 0.03 g/ml) were independent of ␤-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future studies.In recent years, increasing antibiotic resistance among bacteria causing infections within both the hospital and community environments has severely compromised our ability to successfully treat patients empirically. Perhaps nowhere is this more apparent than with patients presenting with communityacquired respiratory tract infections (CA-RTI), in which Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are common pathogens (6). The emergence and dissemination of penicillin-resistant pneumococci are now global phenomena (1,4,14,22,36) and continue to increase. Compounding the problem is the tendency for organisms to also be refractory to some cephalosporins and macrolides (11,42). Similarly, resistance caused by the widespread acquisition of plasmid-encoded BRO1 and/or BRO2 ␤-lactamase in M. catarrhalis and of TEM-1 enzyme in H. influenzae (13, 35) has effectively removed ampicillin and amoxicillin used alone as therapeutic choices for ␤-lactamase-producing isolates, neither being stable in the presence of those enzymes. Together, these factors have created a need for alternative oral candidate drugs for use as empiric therapies for patients with CA-RTI.Recently, the further evolution of the fluoroquinolone class of drugs has resulted in a number of new compounds with an expanded spectrum of activity compared with earlier compounds such as ciprofloxacin and ofloxacin, most significantly against S. pneumo...

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 62%

Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

Jones

Staples²,

Critchley³

et al. 2000

Antimicrob Agents Chemother

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“…Second-step mutants selected had either a second mutation in ParC or in ParE. Moxifloxacin could belong to these fluoroquinolones, which preferentially target GyrA though probably acting equally through both gyrase and topoisomerase IV.Moxifloxacin (MXF) is an 8-methoxyquinolone very active against penicillin-susceptible as well as penicillin-resistant Streptococcus pneumoniae (2,14), with MICs at which 90% of the isolates tested are inhibited ranging from 0.12 to 0.25 g/ml. If resistance of S. pneumoniae to fluoroquinolones (FQs) appears still very low (3,4,14), in the clinical setting resistant mutants have nevertheless been described that harbor different mutations in topoisomerase IV and gyrase either alone or associated (3,(12)(13)(14)(15).…”

mentioning

confidence: 99%

Topoisomerase Mutations Associated with In Vitro Selection of Resistance to Moxifloxacin in Streptococcus pneumoniae

Houssaye

Gutmann

Varon

2002

Antimicrob Agents Chemother

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We analyzed the frequencies of selection, the order of acquisition, and the mutations selected on moxifloxacin in two wild-type pneumococcal strains, R6 and 5714. The first selection step showed either a single GyrA mutation or no mutation in any of the quinolone resistance-determining regions. Second-step mutants selected had either a second mutation in ParC or in ParE. Moxifloxacin could belong to these fluoroquinolones, which preferentially target GyrA though probably acting equally through both gyrase and topoisomerase IV.Moxifloxacin (MXF) is an 8-methoxyquinolone very active against penicillin-susceptible as well as penicillin-resistant Streptococcus pneumoniae (2,14), with MICs at which 90% of the isolates tested are inhibited ranging from 0.12 to 0.25 g/ml. If resistance of S. pneumoniae to fluoroquinolones (FQs) appears still very low (3,4,14), in the clinical setting resistant mutants have nevertheless been described that harbor different mutations in topoisomerase IV and gyrase either alone or associated (3,(12)(13)(14)(15). Several studies have established that FQs can be grouped in at least two main classes (7, 9,10). The first class, including levofloxacin, pefloxacin, ciprofloxacin, and trovafloxacin, will select quinolone resistance-determining region (QRDR) mutations first in topoisomerase IV and then in gyrase. The second group, including sparfloxacin, gemifloxacin, gatifloxacin, clinafloxacin, and BMS-284756, will select mutations first in gyrase and then in topoisomerase IV. No FQ able to target either topoisomerase IV or gyrase at the first selection step in S. pneumoniae has been described so far, but that fact does not exclude that both enzymes may simultaneously contribute to the activity of a defined FQ (9, 10, 18). In a previous study (22) it was shown, using isogenic transformants harboring different mutations in the QRDR of the ParC subunit of the topoisomerase IV or of the GyrA subunit of the gyrase, that a similar low level of resistance was obtained for MXF, although this did not indicate if a preferential target existed. In this study, using a stepwise selection method, we demonstrated in the presence of MXF the order of acquisition and the type of mutations in the QRDR of the topoisomerase genes for two strains of S. pneumoniae.S. pneumoniae R6 is a susceptible derivative of the encapsulated Rockefeller University strain R36A; 5714 is an FQsusceptible clinical isolate of S. pneumoniae (11). For the first selection step, 10 9 to 10 10 cells were plated onto MuellerHinton agar supplemented with 5% horse blood containing various concentrations of MXF or levofloxacin and were incubated aerobically for 48 to 72 h. Colonies were restreaked on plates containing the same drug concentration. The next selection step was done in the same manner using one of the mutants selected during the first step. Frequencies of resistant mutants were calculated from the ratio of the count of CFU obtained on drug-containing plates to the count of CFU obtained on drug-free plates. MICs were determined in ...

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“…Gli studi microbiologici sono stati condotti su raccolte di ceppi d'isolamento clinico comprendenti batteri Gram-positivi, Gram-negativi, anaerobi, patogeni atipici . La maggior parte delle ricerche microbiologiche ha focalizzato l'attenzione sui patogeni respiratori, nei confronti dei quali la moxifloxacina ha dimostrato di avere un'elevata attività battericida [31][32][33][34][35][36][37][38].…”

Section: Profilo Microbiologicounclassified

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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Benchmarking the in vitro activity of moxifloxacin against recent isolates of Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. A European multi-centre study

Cited by 22 publications

References 28 publications

Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

Topoisomerase Mutations Associated with In Vitro Selection of Resistance to Moxifloxacin in Streptococcus pneumoniae

Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomico

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