Disease relevance of sparfloxacin

• The fluoroquinolone antibiotics sparfloxacin, grepafloxacin, gatifloxacin, and levofloxacin have been reported to cause torsades de pointes [1].
• In this article we review the toxicity of fluoroquinolones, including the newer derivatives such levofloxacin, sparfloxacin, graepafloxacin and the 7-azabicyclo derivatives, trovafloxacin and moxifloxacin [2].
• Powerful bactericidal activity of sparfloxacin (AT-4140) against Mycobacterium tuberculosis in mice [3].
• To investigate this idea, we have studied the response of Staphylococcus aureus RN4220 to stepwise challenge with sparfloxacin, a known dual-target agent, and with NSFQ-105, a more potent sulfanilyl fluoroquinolone that behaves similarly [4].
• In vivo efficacy of a new fluoroquinolone, sparfloxacin, against penicillin-susceptible and -resistant and multiresistant strains of Streptococcus pneumoniae in a mouse model of pneumonia [5].

High impact information on sparfloxacin

• Block of HERG by sparfloxacin displayed a positive voltage dependence [6].
• Sparfloxacin was the most potent compound, displaying an IC50 value of 18 microM, whereas ofloxacin was the least potent compound, with an IC50 value of 1420 microM [6].
• Isolates resistant to sparfloxacin and levofloxacin included MRSA, enterococci, and some anaerobes [7].
• MICs for Mycobacterium tuberculosis H37Rv were 0.1 mg/liter (sparfloxacin [SPX]) and 0.5 mg/liter (moxifloxacin [MXF], ciprofloxacin [CIP], and ofloxacin [OFX]) [8].
• The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin [9].

Chemical compound and disease context of sparfloxacin

• Efficacy and safety of single oral dose sparfloxacin vs ciprofloxacin in acute gonococcal urethritis in males. A multicentre international study [10].
• A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria [11].
• Against gram-negative bacteria, the activity of CS-940 was comparable to or greater than those of tosufloxacin, sparfloxacin, and levofloxacin, while it was lower than that of ciprofloxacin [12].
• Mycoplasma pneumoniae was as susceptible to trovafloxacin (MIC = 0.25 microgram/ml) as to sparfloxacin and fourfold less susceptible to ofloxacin [13].
• We studied the activities of the new fluoroquinolones clinafloxacin, levofloxacin, ofloxacin, and sparfloxacin alone or in combination on the intracellular growth of Listeria monocytogenes [14].

Biological context of sparfloxacin

• Chondrotoxicity and toxicokinetics of sparfloxacin in juvenile rats [15].
• Antacids containing aluminium hydroxide reduce the oral bioavailability of sparfloxacin by 25 to 35% [16].
• The drugs were injected at doses which mimicked the kinetics in human serum produced by one intravenous injection of 400 mg of sparfloxacin (i.e., the daily dose expected to be given to human adults) and 2 g of ceftriaxone [17].
• Recombinant plasmid pGADIV was selected from a genomic library of wild-type (WT), FQ-sensitive M. smegmatis by its ability to confer low-level resistance to sparfloxacin (SPX) [18].
• Sparfloxacin binds weakly to plasma protein (37%), and exhibits excellent tissue distribution and effective penetration into extracellular fluids [16].

Anatomical context of sparfloxacin

• Despite their anticipated markedly higher intracellular human neutrophil (PMN) concentrations, RP 59500 and sparfloxacin activities in medium alone were equal to or greater than those inside PMNs against almost all strains [19].
• These data suggest that a once-daily, 3-day regimen of sparfloxacin is effective and generally well tolerated in the treatment of acute uncomplicated urinary tract infections [20].
• The unidirectional fluxes across cell monlayers grown on permeable filters indicated that a net secretion of sparfloxacin and vinblastine occurred across Caco-2 cells [21].
• Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages [22].
• The mechanism of intestinal secretion of the difluorinated quinolone sparfloxacin was investigated with the epithelial cell line Caco-2 and was compared to that of the P-glycoprotein (P-gp) substrate vinblastine [21].

Associations of sparfloxacin with other chemical compounds

• Active levels of sparfloxacin, temfloxacin, or ciprofloxacin were continuously present in tissue cage fluid during therapy, exceeding their MBCs for MRSA by 6- to 20-fold [23].
• Against S. pneumoniae, garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than by a single parC mutation [24].
• The hydrophobicity of tosufloxacin was nearly equal to that of ofloxacin or lower than those of sparfloxacin and nalidixic acid [25].
• The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with potent antibacterial activity, were compared with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin [26].
• Multicenter evaluation of the in vitro activities of three new quinolones, sparfloxacin, CI-960, and PD 131,628, compared with the activity of ciprofloxacin against 5,252 clinical bacterial isolates [27].

Gene context of sparfloxacin

• A gyrA mutation in TKp1 secondary mutants was associated with 32- to 128-fold increases in the MICs of ofloxacin and ciprofloxacin compared with the MICs for H37Ra and an eight-fold increase in the MIC of sparfloxacin [28].
• gyrA and parC mutations have been identified inn Streptococcus pneumoniae mutants stepwise selected for resistance to sparfloxacin, an antipneumococcal fluoroquinolone [29].
• The MICs of moxifloxacin for Campylobacter coli and Campylobacter jejuni strains with a gyrA mutation leading to Thr86-->Ile substitution ranged from 1 to 2 mg/L, while the MICs of ciprofloxacin, ofloxacin and sparfloxacin were 16-32 mg/L, 8-16 and 4-8 mg/L, respectively [30].
• Sensitivity to sparfloxacin and other antibiotics, of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis strains isolated from adult patients with community-acquired lower respiratory tract infections: a European multicentre study. SPAR Study Group. Surveillance Programme of Antibiotic Resistance [31].
• Sparfloxacin, a P-glycoprotein substrate, also significantly decreased the renal and tubular secretion clearances of pazufloxacin, suggesting that pazufloxacin and sparfloxacin share the same transporters, including P-glycoprotein [32].

Analytical, diagnostic and therapeutic context of sparfloxacin

• Plasma and urine samples were collected up to 144 h postdosing for determination of parent and total (parent-plus-glucuronide-conjugated) sparfloxacin levels, by high-pressure liquid chromatography assay and UV detection [33].
• Ciprofloxacin, ofloxacin, levofloxacin and sparfloxacin are currently the most commonly used agents used against Mycobacterium tuberculosis (TB), with in vitro minimum inhibitory concentrations (MICs) of 0.1 to 4 mcg/ml [34].
• Four hundred nineteen women were enrolled in a randomized, open-label, observer-blinded, multicenter study; 204 received sparfloxacin as a 400-mg loading dose on the first day and 200 mg once daily thereafter, and 215 received ofloxacin as 200 mg twice daily [20].
• The profile of adverse effects for sparfloxacin is generally similar to that of other quinolones: gastrointestinal discomfort and CNS effects are the most common in clinical trials [35].
• Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay [36].

References