In vitro activity of tosufloxacin (A-61827; T-3262) against selected genital pathogens

Segreti, John; Hirsch, Dania; Harris, Angelique; Kapell, K S; Orbach, H; Kessler, Harold A.

doi:10.1128/aac.34.6.971

Cited by 11 publications

(3 citation statements)

References 9 publications

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“…In vitro susceptibility testing has clearly indicated successful suppression of chlamydial growth by both drugs, as demonstrated by a MIC and MBC of 0.35 g/ml for ciprofloxacin and 0.5 g/ml for ofloxacin. These results are in good accord with those published by others (4,7,22,28,38,42,44,45,46,49). Treatment failures observed for ciprofloxacin, however, present an apparent contradiction to results of determination of MIC and MBC, whereas data of ofloxacin appeared to be consistent.…”

Section: Discussionsupporting

confidence: 75%

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Persistence ofChlamydia trachomatisIs Induced by Ciprofloxacin and Ofloxacin In Vitro

Dreses-Werringloer

Padubrin

Jürgens‐Saathoff

et al. 2000

Antimicrob Agents Chemother

113

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An in vitro cell culture model was used to investigate the long-term effect of ciprofloxacin and ofloxacin on infection with Chlamydia trachomatis. Standard in vitro susceptibility testing clearly indicated successful suppression of chlamydial growth. To mimic better in vivo infection conditions, extended treatment with the drugs was started after infection in vitro had been well established. Incubation of such established chlamydial cultures with ciprofloxacin and ofloxacin not only failed to eradicate the organism from host cells, but rather induced a state of chlamydial persistence. This state was characterized by the presence of nonculturable, but fully viable, bacteria and the development of aberrant inclusions. In addition chlamydia exhibited altered steadystate levels of key chlamydial antigens, with significantly reduced major outer membrane protein and near constant hsp60 levels. Resumption of overt chlamydial growth occurred after withdrawal of ciprofloxacin, confirming the viability of persisting chlamydia. In vitro ciprofloxacin results are consistent with clinical data, thereby providing an explanation for treatment failures of ciprofloxacin. Parallel in vitro studies with ofloxacin suggest a better correlation between clinical and laboratory-defined efficacy, although the clinical studies on which this assessment is based did not include monitoring of chlamydial persistence. The data presented here clearly demonstrate that under at least some circumstances, standard determination of MICs and minimal bactericidal concentrations for C. trachomatis allows no more than a simple definition of whether an antibiotic has some anti chlamydial activity; however, such testing is not always sufficient to verify that the antibiotic will eliminate the organism in vivo.Chlamydia trachomatis is an obligate intracellular bacterial parasite whose life cycle involves alternation between the infectious extracellular, metabolically inactive elementary body (EB) form and the intracellular, metabolically active reticulate body form; the latter is the vegetative growth stage of the organism. Depending on the specific serovar involved, human infection with C. trachomatis causes a variety of ocular, pulmonary, and genital diseases. Genital infection with chlamydial serovars D to K is considered to be of major public health importance, since C. trachomatis is the most common sexually transmitted bacterium worldwide (54). Further, acute urogenital infections can progress to persistent infection, which in turn may initiate a pathogenic process leading to chronic diseases, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and chlamydia-induced arthritis (12, 53). Importantly, C. trachomatis has been shown to be fully viable and metabolically active in both the acute and chronic, persistent infection state. In acute infections, the bacterium can be recovered usually by standard laboratory culture. Chronic chlamydial infections are often characterized by culture negativity, although viability has...

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Section: Discussionsupporting

confidence: 75%

“…For C. trachomatis, such in vitro susceptibility testing indicated good activity for ciprofloxacin (22,38,45,46,49). However, in clinical trials a high rate of treatment failure has been observed with this drug.…”

mentioning

confidence: 99%

Persistence ofChlamydia trachomatisIs Induced by Ciprofloxacin and Ofloxacin In Vitro

Dreses-Werringloer

Padubrin

Jürgens‐Saathoff

et al. 2000

Antimicrob Agents Chemother

113

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“…The activities of these drugs against C. pneumoniae appear to be similar to those reported for C. trachomatis (11 (2). Although the MICs of the other drugs, including ofloxacin and temafloxacin, are almost 10-fold higher, they are well within achievable serum levels.…”

supporting

confidence: 50%

In vitro activities of five quinolones against Chlamydia pneumoniae

Hammerschlag

Hyman

Roblin

1992

Antimicrob Agents Chemother

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The in vitro susceptibilities of 10 strains of Chlamydia pneumoniae were determined for five quinolones, including ciprofloxacin, ofloxacin, fleroxacin, temafloxacin, and sparfloxacin. Sparfloxacin was the most active compound tested, followed by ofloxacin and temafloxacin. Ciprofloxacin and fleroxacin were the least active. The use of HEp-2 cells for testing C. pneumoniae resulted in larger inclusions but essentially the same endpoints as were seen with use of HeLa 229 cells.Chlamydia pneumoniae, the newly described chlamydial species, is emerging as a frequent cause of communityacquired respiratory tract infections, including pneumonia and bronchitis (1,5

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The Role of Fluoroquinolones in Sexually Transmitted Diseases

Tartaglione,

Hooton

1993

Pharmacotherapy

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The management of sexually transmitted diseases (STDs) has reached a new level in the era of antibiotic resistance and human immunodeficiency virus infection. To date, no single antimicrobial is capable of eradicating the commonly encountered STD pathogens including Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. Among the marketed fluoroquinolones, ciprofloxacin, ofloxacin, lomefloxacin, and enoxacin all provide excellent in vitro activity (MIC90 < 0.06 μg/ml) and excellent in vivo efficacy against N. gonorrhoeae, including multiply resistant isolates (penicillinase‐producing N. gonorrhoeae and chromosomally mediated resistant N. gonorrhoeae). Ofloxacin is the only fluoroquinolone approved by the Food and Drug Administration for chlamydial infection. All of the quinolones lack reliable in vitro activity against Ureaplasma urealyticum, a cause of nongonococcal urethritis. Although limited data suggest the usefulness of ciprofloxacin and ofloxacin in the treatment of pelvic inflammatory disease, these drugs cannot currently be recommended for single‐agent therapy. Haemophilus ducreyi infections, however, can be managed effectively with the fluoroquinolones. Although their role continues to evolve, this class of drugs cannot be used equally to treat all STDs, and notably, no quinolone to date inhibits T. pallidum.

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In vitro activity of tosufloxacin (A-61827; T-3262) against selected genital pathogens

Cited by 11 publications

References 9 publications

Persistence ofChlamydia trachomatisIs Induced by Ciprofloxacin and Ofloxacin In Vitro

Persistence ofChlamydia trachomatisIs Induced by Ciprofloxacin and Ofloxacin In Vitro

In vitro activities of five quinolones against Chlamydia pneumoniae

The Role of Fluoroquinolones in Sexually Transmitted Diseases

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