Abstract:
:The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were evaluated over 24 to 48 h against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA 1199 and MRSA 494, respectively) in an in vitro infection model. The incidence of the emergence of resistance among the test strains was also determined. The fluoroquinolones were administered to simulate dosage regimens of 200 mg, 400 mg given intravenously (i.v.) every 12 h (q12h), and 400 and 800 mg given i.v. q24h. Rifampin was dosed at 600 mg i.v. q24h. Although the MICs and MBCs of the quinolones were similar (< or = 0.49 microgram/ml), levofloxacin was the most potent agent in time-kill studies on the basis of the time required to achieve a 99.9% reduction in the number of log10 CFU per milliliter (e.g., with the regimen of levofloxacin [400 mg q24h, 6.5 h] versus ofloxacin [12.5 h], P < 0.024, and levofloxacin versus ciprofloxacin [6.5 versus 9.0 h], P < 0.0017) against MSSA 1199. The killing activity of levofloxacin was similar to that of ofloxacin against MRSA 494 (time to achieve a 99.9% reduction in the number of log10 CFU per milliliter, 11.1 versus 13.8 h, respectively). Levofloxacin and ofloxacin dosed once daily demonstrated greater bactericidal activity than when they were dosed twice daily against MSSA 1199. Resistance to levofloxacin or ofloxacin was not observed with any dosage regimen. Furthermore, resistance to ofloxacin was not detected when the half-life was reduced from 6 to 3 h. Regrowth and stable resistance (65-fold increase in the MIC for MSSA 1199; 16-fold increase in the MIC for MRSA 494) were noted within 24 h of exposure to ciprofloxacin at 200 mg q12h. Combination therapy with rifampin prevented the emergence of resistance to ciprofloxacin. Neither DNA gyrase alteration nor an energy-dependent efflux process mediated by the norA gene appeared to be responsible for the resistance observed. Our data suggest that with levofloxacin there is a more rapid onset of bactericidal activity than with ofloxacin or ciprofloxacin against MSSA 1199 and that the activity of levofloxacin is similar to that of ofloxacin but better than that of ciprofloxacin against MRSA 494. Resistance was noted only after exposure to the low dose of ciprofloxacin. Resistance to ofloxacin did not develop even when the pharmacokinetics of the drug were set to equal those of ciprofloxacin, suggesting that ofloxacin differs from ciprofloxacin irrespective of time of exposure. The resistance to ciprofloxacin that developed in our vitro model may be mediated by the cfx-ofx locus, which has been shown to be associated with low-level fluoroquinolone resistance. Overall, levofloxacin demonstrated potent bactericidal activity against S. aureus, without the emergence of resistance in our infection model. Quinolones dosed once daily were more effective than equivalent dosages administered twice daily. The addition of rifampin was not synergistic but prevented the emergence of ciprofloxacin resistance.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Kang SL,Rybak MJ,McGrath BJ,Kaatz GW,Seo SMdoi
10.1128/aac.38.12.2702subject
Has Abstractpub_date
1994-12-01 00:00:00pages
2702-9issue
12eissn
0066-4804issn
1098-6596journal_volume
38pub_type
杂志文章abstract::A global sample of group A streptococci (GAS) revealed > or =80 separate acquisitions of tetracycline resistance. Of 244 clones, 38 and 25% displayed resistance to tetracycline and erythromycin, respectively; a relatively high proportion (15%) were resistant to both classes of drugs. tet(M) displayed a highly signific...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01341-06
更新日期:2007-05-01 00:00:00
abstract::The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.1.31
更新日期:1983-01-01 00:00:00
abstract::We sought to determine whether there was an interaction between aminoglycoside use and shock in their effect on renal function among seriously ill patients suspected of having gram-negative sepsis. Serial serum creatinine determinations were used to estimate changes in creatinine clearance rates in 179 patients entere...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.27.2.217
更新日期:1985-02-01 00:00:00
abstract::Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal componen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.1.27
更新日期:1987-01-01 00:00:00
abstract::Of 3,004 gram-negative bacilli collected from intra-abdominal infections in the Asia-Pacific region during 2007, 42.2% and 35.8% of Escherichia coli and Klebsiella spp., respectively, were extended-spectrum beta-lactamase (ESBL) positive. Moreover ESBL rates in India for E. coli, Klebsiella pneumoniae, and Klebsiella ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00426-09
更新日期:2009-08-01 00:00:00
abstract::We compared a rigid (1-h) screening method for the detection of chloramphenicol acetyltransferase (CAT) activity with the standard spectrophotometric CAT assay to determine whether CAT-mediated chloramphenicol resistance in Haemophilus influenzae could be determined upon primary isolation. Of 58 H. influenzae cell son...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.2.168
更新日期:1981-08-01 00:00:00
abstract::In 1989 and 1990, a large number of ampicillin-resistant strains of Enterococcus faecium were isolated from infected patients treated at intensive care units in Berlin, Germany. Twenty-five clinical isolates, including five different biotypes as classified by acid production from various sugars and a wide range of sus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.4.783
更新日期:1992-04-01 00:00:00
abstract::The current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05646-11
更新日期:2012-02-01 00:00:00
abstract::Bradyzoite-to-tachyzoite conversion plays a role in the pathogenesis of recrudescence of ocular toxoplasmosis and disease in immunocompromised persons. The currently available medicines are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. A previous study showed that the histone deacetyla...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00462-10
更新日期:2010-11-01 00:00:00
abstract::Mycobacterium tuberculosis strains with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. Fourteen newly diagnosed tuberculosis patients were treated with RIF alone for 14 days, and bacterial loa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.02220-16
更新日期:2017-03-24 00:00:00
abstract::Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M. intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals. Against the i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1390
更新日期:1990-07-01 00:00:00
abstract::In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.1124
更新日期:1997-05-01 00:00:00
abstract::The serum pharmacokinetic profile of intravenous (i.v.) tobramycin administration was characterized for a sample of nine adult patients with cystic fibrosis (CF) who were hospitalized for an acute pulmonary exacerbation. Current recommended i.v. tobramycin dosing protocols are predicted through modeling and simulation...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00539-13
更新日期:2013-10-01 00:00:00
abstract::Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), has surpassed HIV/AIDS as the leading cause of death from a single infectious agent. The increasing occurrence of drug-resistant strains has become a major challenge for health care systems and, in some cases, has rendered TB untreatable. Howe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01846-18
更新日期:2019-01-29 00:00:00
abstract::Clostridium difficile is the leading cause of hospital-acquired infectious diarrhea. LFF571 is a novel inhibitor of the prokaryotic translation elongation factor Tu and is active against a range of bacterial species, including C. difficile. This first-in-human study investigated the safety and pharmacokinetics of sing...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00867-12
更新日期:2012-11-01 00:00:00
abstract::Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.6.837
更新日期:1984-12-01 00:00:00
abstract::The efficacies of ciprofloxacin and ampicillin against Listeria monocytogenes in an immunosuppressed mouse model of listeriosis were compared. Immunosuppression was achieved by administration of 2.5 mg of hydrocortisone acetate daily. Both ciprofloxacin and ampicillin were effective in reducing the number of viable L....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.11.2375
更新日期:1992-11-01 00:00:00
abstract::The current recommendations for intravenous (i.v.) acyclovir dosing in obese patients suggest using ideal body weight (IBW) rather than total body weight (TBW). To our knowledge, no pharmacokinetic analysis has validated this recommendation. This single-dose pharmacokinetic study was conducted in an inpatient oncology...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.02010-15
更新日期:2016-01-11 00:00:00
abstract::Recent evidence supports the contribution of a multidrug efflux mechanism to fluoroquinolone resistance in Streptococcus pneumoniae. In this paper I show that reserpine, an inhibitor of multidrug transporters in gram-positive bacteria, dramatically suppresses the in vitro emergence of ciprofloxacin-resistant variants ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.4.988
更新日期:1999-04-01 00:00:00
abstract::Blastocystis is an enteric parasite with extensive global prevalence. Studies have linked infection with this protist with a variety of gastrointestinal disorders, including irritable bowel syndrome. Due to the polymorphic nature of Blastocystis, studies on the parasite could be complicated, as results can be easily m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00208-18
更新日期:2018-07-27 00:00:00
abstract::Standard therapy of human visceral leishmaniasis with parenteral pentavalent antimonial agents is generally curative but has the disadvantages of a 28-day treatment course, occasional treatment failures, and toxicity. The antifungal and antileishmanial agent amphotericin B has been complexed with lipids to develop a l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.9.1978
更新日期:1992-09-01 00:00:00
abstract::The pharmacokinetics of cefmenoxime were characterized in five healthy volunteers and in 15 subjects with various degrees of renal insufficiency after a single 10-mg/kg, 5-min intravenous infusion. Five of these subjects were studied both on hemodialysis and during an interdialytic period. Plasma, urine and dialysate ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.6.845
更新日期:1984-12-01 00:00:00
abstract::We have quantified the biological cost of VanA-type glycopeptide resistance due to the acquisition of the resistance operon by methicillin-resistant Staphylococcus aureus (MRSA) from Enterococcus sp. Exponential growths of recipient strain HIP11713, its transconjugant VRSA-1, VRSA-5, and VRSA-6 were compared in the ab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01702-08
更新日期:2009-06-01 00:00:00
abstract::With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02223-16
更新日期:2017-06-27 00:00:00
abstract::We investigated differences in the clinical findings between 30 patients with macrolide-resistant Mycoplasma pneumoniae pneumonia and 43 patients with macrolide-sensitive M. pneumoniae pneumonia in adolescents and adults. No differences in clinical presentation were observed between the two groups. Among patients with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00737-13
更新日期:2013-10-01 00:00:00
abstract::The multiple antibiotic resistance (mar) locus in Escherichia coli consists of two divergently expressed operons (marC and marRAB), both of which contribute to the Mar phenotype. Overexpression of the marRAB operon protected E. coli against rapid cell killing by fluoroquinolones. Inactivation of the operon in mar muta...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1266
更新日期:1996-05-01 00:00:00
abstract::Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.50.2.632-638.2006
更新日期:2006-02-01 00:00:00
abstract::Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01730-13
更新日期:2014-08-01 00:00:00
abstract::In a single quantitative study, we measured acrA, acrB, tolC, mdfA, and norE expression in Escherichia coli clinical isolates by using real-time PCR. acrA and acrB overexpression strongly correlated with fluoroquinolone and multidrug resistance; tolC, mdfA, and norE expression did not. The order of abundance of efflux...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00996-10
更新日期:2011-02-01 00:00:00
abstract::In 2009, the first high-level ceftriaxone-resistant Neisseria gonorrhoeae strain (H041) was isolated in Kyoto, Japan. The present study describes an intensified surveillance (antimicrobial resistance and molecular typing) of Neisseria gonorrhoeae isolates in Kyoto and its neighboring prefecture Osaka, Japan, in 2010 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01295-13
更新日期:2013-11-01 00:00:00