Abstract:
:The single- and multiple-dose pharmacokinetics of and tolerability to a new microfluidized suspension of atovaquone were studied in human immunodeficiency virus-seropositive patients with CD4 counts of < or = 200 cells per mm3 in order to define a dosing regimen for the treatment of Pneumocystis carinii pneumonia. This was an open study with groups of six patients each. In the first part of the study, six subjects received escalating single doses of 500, 1,000, and 1,500 mg after an overnight fast at weekly intervals. In the second part of the study, groups of six subjects were dosed for 14 days according to three regimens: 1,000 mg twice daily fasting, twice daily with a high-fat meal, or once daily with a high-fat meal. Plasma atovaquone levels were assayed by high-performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental methods, and statistical comparison of parameters for single doses was performed by analysis of variance. Plasma drug concentrations increased with single doses from 500 to 1,000 mg but were no higher with a dose of 1,500 mg. Thus, 1,000 mg was selected for multiple administration. A regimen of 1,000 mg twice daily with food resulted in a 93% increase in the average trough steady-state concentration compared with 1,000 mg once daily with food. Food increased the bioavailability of atovaquone 1.4-fold over that in the fasting state. All patients who received 1,000 mg twice daily with food achieved target steady-state concentrations in plasma of 15 to 25 micrograms/ml. Multiple-dose regimens were generally well tolerated, but the higher levels in plasma achieved by 1,000 mg twice daily with food were associated with an increased incidence of rash. In conclusion, target plasma atovaquone concentrations for the treatment of P. carinii pneumonia can be achieved in most patients with 1,000 mg twice daily in a fasting state and in all patients with 1,000 mg twice daily administered with food, but at higher concentrations in plasma, there may be an increased risk of rash.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Dixon R,Pozniak AL,Watt HM,Rolan P,Posner Jdoi
10.1128/AAC.40.3.556subject
Has Abstractpub_date
1996-03-01 00:00:00pages
556-60issue
3eissn
0066-4804issn
1098-6596journal_volume
40pub_type
临床试验,杂志文章abstract::We recently reported that HIV-1 resistant to 3'-azido-3'-deoxythymidine (AZT) is not cross-resistant to 3'-azido-2',3'-dideoxypurines. This finding suggested that the nucleoside base is a major determinant of HIV-1 resistance to nucleoside analogs. To further explore this hypothesis, we conducted in vitro selection ex...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00414-11
更新日期:2011-08-01 00:00:00
abstract::We describe a primary high-throughput screen that uses the reporter strain Bacillus subtilis BAU-102 to identify antibiotics that induce autolysis. The screen measures autolysis in terms of the incipient release of recombinant Escherichia coli beta-galactosidase (beta-Gal) from the periplasmic space of B. subtilis owi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01597-09
更新日期:2010-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01101-15
更新日期:2015-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05438-11
更新日期:2012-02-01 00:00:00
abstract::Azole antifungal resistance in Aspergillus fumigatus is a worldwide concern. As in most public hospitals in Brazil, antifungal susceptibility tests are not routinely performed for filamentous fungi at our institution. A 4-year retrospective azole antifungal resistance screening revealed two azole-resistant A. fumigatu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02059-19
更新日期:2020-02-21 00:00:00
abstract::Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are an important cause of morbidity and mortality in hospital patients. Moreover, increased incidences of outpatient MRSA have been recently reported. This study investigated the bactericidal activity of dalbavancin, a novel, semisynthetic glycopepti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.4.1118-1123.2004
更新日期:2004-04-01 00:00:00
abstract::Hard-tick-borne relapsing fever (HTBRF) is an emerging infectious disease throughout the temperate zone caused by the relapsing-fever spirochete Borrelia miyamotoi Antibiotic treatment of HTBRF is empirically based on the treatment of Lyme borreliosis; however, the antibiotic susceptibility of B. miyamotoi has not bee...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00535-17
更新日期:2017-08-24 00:00:00
abstract::Vancomycin pharmacokinetics were studied in four patients with peritonitis undergoing chronic intermittent peritoneal dialysis. Serum levels exceeding 4.0 micrograms/ml were maintained for 8 and 13 days after a single 1-g intravenous dose. Vancomycin serum concentrations measured before, during, and upon completion of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.5.710
更新日期:1983-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.11.4437-4442.2005
更新日期:2005-11-01 00:00:00
abstract::A simple technique for routine, reproducible global surveillance of the drug susceptibility status of the anaerobic protozoa Trichomonas, Entamoeba, and Giardia is described. Data collected using this technique can be readily compared among different laboratories and with previously reported data. The technique employ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.6.1810-1814.2001
更新日期:2001-06-01 00:00:00
abstract::We have shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. We studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (CNS) aspergillosis to assess early event...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06015-11
更新日期:2012-08-01 00:00:00
abstract::Oral administration of 2'-deoxy-3'-oxa-4'-thiocytidine (BCH-10652), a nucleoside analog structurally similar to lamivudine (3TC), caused dose-dependent inhibition of viral replication in SCID-hu Thy/Liv mice infected with human immunodeficiency virus type 1 NL4-3 and with an NL4-3 clone containing the M184V mutation i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.3.783-786.2000
更新日期:2000-03-01 00:00:00
abstract::The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.1.73
更新日期:1977-07-01 00:00:00
abstract::Fenpropimorph was shown to inhibit the accumulation of the pyrimidine bases uracil and cytosine from the growth media in Saccharomyces cerevisiae. Uracil prototrophs of S. cerevisiae were more resistant to the growth-inhibitory effects of fenpropimorph than were uracil auxotrophs. High concentrations of uracil rescued...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.5.1004
更新日期:1994-05-01 00:00:00
abstract::beta-Lactamases from Aeromonas hydrophila and A. sobria were purified and characterized. Both species produced beta-lactamases that were inducible by either cefoxitin or imipenem. These species were resistant to ampicillin and cephalothin but not imipenem. Isoelectric focusing of sonic extracts revealed one band at pI...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.1.44
更新日期:1990-01-01 00:00:00
abstract::Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions, such as thrombocytopenia, when standard-dose linezolid is used than patients with LD who did not use linezolid. Curre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00133-20
更新日期:2020-05-21 00:00:00
abstract::CMY-30, a Val211Gly mutant of CMY-2 cephalosporinase, was derived by mutagenesis. The hydrolytic efficiency of CMY-30 against expanded-spectrum cephalosporins was higher than that of CMY-2 due to increased k(cat) values. Findings indicate a role of the Omega loop residue 211 in determining the substrate specificities ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00219-09
更新日期:2009-08-01 00:00:00
abstract::Three mer transposons from the Murray collection of preantibiotic enterobacteria show >99% sequence identity to current isolates. Tn5073 is most closely related to Tn5036 and Tn1696, and Tn5074 is most closely related to Tn5053. Tn5075 is most closely related to Tn21 but lacks integron In2 and is flanked by insertion ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 历史文章,杂志文章
doi:10.1128/aac.47.3.1115-1119.2003
更新日期:2003-03-01 00:00:00
abstract::The in vitro activity of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] was inhibited by CuCl2 with a 50% inhibitory concentration (IC50) of 2.8 μM. The growth of an amikacin-resistant Klebsiella pneumoniae strain isolated from a neonate with meningitis was inhibited when amikacin was supplemented by t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01106-15
更新日期:2015-09-01 00:00:00
abstract::The penam nucleus can assume two conformations; these are designated open and closed. The synthetic (2,3)-alpha- and (2,3)-beta-methylenepenams can be regarded as analogs of the open and closed conformations, respectively. It has been shown that the beta-methylenepenams are essentially inactive, suggesting that the cl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.7.1005
更新日期:1988-07-01 00:00:00
abstract::Mycobacterium abscessus is an extensively drug-resistant opportunistic pathogen that can cause chronic otomastoiditis. There are no evidence-based treatment regimens for this severe infection. We treated four children with M. abscessus otomastoiditis with a structured regimen of topical imipenem and tigecycline, intra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01203-19
更新日期:2019-12-20 00:00:00
abstract::Cecropin B is a cationic antimicrobial peptide originally isolated from the diapausing pupae of the giant silk moth, Hylphora cecropia. Cecropin B elicits its antimicrobial effects through disruption of the anionic cell membranes of gram-negative bacteria. Previous work by our laboratory demonstrated that a constituti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00023-08
更新日期:2008-09-01 00:00:00
abstract::Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01481-06
更新日期:2007-09-01 00:00:00
abstract::The in vitro activities of two investigational quinolones, sparfloxacin (previously designated AT 4140) and PD 127391, were determined for 30 strains each of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ciprofloxacin, tetracycline, clindamycin, and erythromycin. Eryt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1181
更新日期:1991-06-01 00:00:00
abstract::We examined 741 urinary tract isolates of the Morganella-Proteus-Providencia group, including the recently defined species Proteus penneri, for susceptibilities to aminoglycosides, semisynthetic penicillins, and cephalosporins. The data emphasize the importance of identification to the species level on the basis of ma...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1644
更新日期:1987-10-01 00:00:00
abstract::Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02929-15
更新日期:2016-05-23 00:00:00
abstract::To test the hypothesis that establishing gastrointestinal colonization with multiresistant Enterococcus faecium (VRE) C68 results from expansion of the enterococcal population in the upper small bowel, we compared VRE quantities recovered from the proximal, middle, and distal segments of the small bowel from mice trea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00125-06
更新日期:2006-09-01 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::In view of increasing health threats from multiresistant pathogens, antimicrobial peptides (AMPs) and, specifically, proline-rich AMPs (PrAMPs) have been investigated in animal models. PrAMPs enter bacteria via the ABC transporter SbmA and inhibit intracellular targets. We used phage transduction (Tn10 insertion) to s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01307-15
更新日期:2015-10-01 00:00:00
abstract::Stereoselective disposition of sulbenicillin (SBPC) epimers in healthy human volunteers was studied in order to clarify the differences in pharmacokinetic behavior between the epimers. Stereospecific high-performance liquid chromatography was used for the determination of SBPC epimers. Plasma protein binding was measu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00