Abstract:
:The unbound drug hypothesis states that only unbound drug concentrations are active and available for clearance, and highly variable results regarding unbound vancomycin fractions have been reported in the literature. We have determined the unbound vancomycin fractions in four different patient groups by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method and identified factors that modulate vancomycin binding. We have further developed and validated a prediction model to estimate unbound vancomycin concentrations. Vancomycin (unbound and total) concentrations were measured in 90 patients in four different hospital wards (hematology [n = 33 samples], intensive care unit [ICU] [n = 51], orthopedics [n = 44], and pediatrics [age range, 6 months to 14 years; n = 18]) by a validated LC-MS/MS method. Multiple linear mixed model analysis was performed to identify patient variables that were predictive of unbound vancomycin fractions and concentrations. The variables included in the model were patient age, ward, number of coadministered drugs with high protein binding, kidney function (estimated glomerular filtration rate [determined by Chronic Kidney Disease Epidemiology Collaboration formula]), alpha-1-acid glycoprotein, albumin, total bilirubin, IgA, IgM, urea, and total vancomycin concentrations. In the pediatric cohort, the median unbound vancomycin fraction was 81.3% (range, 61.9 to 95.9%), which was significantly higher (P < 0.01) than the unbound fraction found in the three adult patient cohorts (hematology, 60.6% [48.7 to 90.6%]; ICU, 61.7% [47.0 to 87.6%]; orthopedics, 56.4% [45.9 to 78.0%]). The strongest significant predictor of the unbound vancomycin concentration was the total drug concentration, completed by albumin in the pediatric cohort and albumin and IgA in the adult cohorts. Validation of our model was performed with data from 13 adult patients. A mean difference of 0.3 mg/liter (95% confidence interval [CI], -1.3 to 0.7 mg/liter; R(2) = 0.99 [95% CI, 0.95 to 0.99]) between measured and calculated unbound vancomycin concentrations demonstrated that the predictive performance of our model was favorable. Unbound vancomycin fractions vary significantly between pediatric and adult patients. We developed a formula to estimate the unbound fraction derived from total vancomycin, albumin, and IgA concentrations in adult patients.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Oyaert M,Spriet I,Allegaert K,Smits A,Vanstraelen K,Peersman N,Wauters J,Verhaegen J,Vermeersch P,Pauwels Sdoi
10.1128/AAC.01185-15subject
Has Abstractpub_date
2015-11-01 00:00:00pages
7073-9issue
11eissn
0066-4804issn
1098-6596pii
AAC.01185-15journal_volume
59pub_type
杂志文章abstract::Fifty strains of Mycoplasma pneumoniae in L cells were tested for susceptibility to macrolide antibiotics. Rokitamycin, a new macrolide antibiotic, was most active against these organisms, with an MIC for 90% of strains of 0.007 microgram/ml. The MICs of erythromycin, josamycin, and kitasamycin for 90% of strains were...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1843
更新日期:1987-11-01 00:00:00
abstract::Increasingly frequent reports have described the in vivo loss of daptomycin susceptibility in association with clinical treatment failures. The mechanism(s) of daptomycin resistance is not well understood. We studied an isogenic set of Staphylococcus aureus isolates from the bloodstream of a daptomycin-treated patient...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00719-07
更新日期:2008-01-01 00:00:00
abstract::Isolates of Legionella pneumophila serogroup 1, obtained from guinea pigs with experimentally induced Legionnaires disease, were tested for rifampin resistance. Thirteen isolates were from animals treated with rifampin alone, four isolates were from animals treated with saline, and three isolates each were from animal...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.1.5
更新日期:1991-01-01 00:00:00
abstract::Selective decontamination of the digestive tract (SDD) has been evaluated as a method to prevent colonization and infection in ventilated patients in 40 trials. On the basis of an assumption that cross-infection would be reduced as a consequence of SDD and that this would distort the results of SDD studies that used c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,meta分析
doi:10.1128/aac.39.4.941
更新日期:1995-04-01 00:00:00
abstract::In this study, a chromosomally encoded putative drug efflux pump of the SMR family, named AbeS, from a multidrug-resistant strain of Acinetobacter baumannii was characterized to elucidate its role in antimicrobial resistance. Expression of the cloned abeS gene in hypersensitive Escherichia coli host KAM32 resulted in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00748-09
更新日期:2009-12-01 00:00:00
abstract::Few studies have estimated the excess inpatient costs due to nosocomial cultures of Gram-negative bacteria (GNB), and those that do are often subject to time-dependent bias. Our objective was to generate estimates of the attributable costs of the underlying infections associated with nosocomial cultures by using a uni...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00462-18
更新日期:2018-10-24 00:00:00
abstract::Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00028-18
更新日期:2018-05-25 00:00:00
abstract::MUC7 12-mer-L exhibits potent in vitro antifungal activity in low-ionic-strength buffers. In this study, we investigated the anticandidal activity and stability of MUC7 12-mer-L and its all-D-amino-acid isomer, along with Hsn5 12-mer (P113) and magainin-II, in human clarified and unclarified saliva in the absence or p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.6.2336-2342.2005
更新日期:2005-06-01 00:00:00
abstract::Histoplasmosis is a severe infection that affects millions of patients worldwide and is endemic in the Americas. Amphotericin B (AMB) and itraconazole are highly effective for the treatment of severe and milder forms of the disease, but AMB is toxic, and the bioavailability of itraconazole is erratic. Therefore, it is...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01654-13
更新日期:2014-05-01 00:00:00
abstract::Sixteen clinical fungal isolates were tested for antibiotic susceptibility by using disks impregnated with growth medium and antibiotic. The procedure was easier to perform, less time consuming, and as reliable as other currently available methods. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.6.1070
更新日期:1976-06-01 00:00:00
abstract::Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Le...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00496-12
更新日期:2012-11-01 00:00:00
abstract::The responses of 20 ampicillin-susceptible Haemophilus influenzae type b clinical isolates to the bactericidal action of ampicillin were studied by using a modified agar dilution plate count method. A well-defined paradoxical effect was observed in each of the 24-h killing curve patterns for 19 of the 20 isolates, the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1711
更新日期:1987-11-01 00:00:00
abstract::Ethambutol (EMB) is a major component of the first-line therapy of tuberculosis. Mutations in codon 306 of embB (embB306) were suggested as a major resistance mechanism in clinical isolates. To directly analyze the impact of individual embB306 mutations on EMB resistance, we used allelic exchange experiments to genera...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00007-10
更新日期:2011-06-01 00:00:00
abstract::The apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children and immunocompromised individuals, with the only FDA-approved drug treatment currently being nitazoxanide. The existing therapies for toxoplasmosis, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00873-16
更新日期:2016-09-23 00:00:00
abstract::Using a real-time PCR assay specific for a mosaic penA allele that has been associated with oral cephalosporin resistance in Asia, 54 available Neisseria gonorrhoeae isolates collected in San Francisco, CA, from January to October 2008 were analyzed. Five isolates tested positive for the mosaic penA gene by real-time ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00406-09
更新日期:2009-09-01 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::Two specific inhibitors of herpes simplex virus thymidine kinase, N2-phenyl-2'-deoxyguanosine and N2-(m-trifluoromethylphenyl)guanine, were tested for their ability to inhibit the reactivation of virus from explant cultures of latently infected murine trigeminal ganglia. Both compounds significantly diminished the fre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.1285
更新日期:1990-06-01 00:00:00
abstract::Clindamycin was given intravenously to 15 patients undergoing colorectal surgery in an initial dose of 600 mg, given at induction of anesthesia followed by 6 doses of 600 mg at 8-h intervals. Series of serum samples and fecal specimens were taken for analysis of clindamycin concentrations. Tissue samples from the gut ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.6.736
更新日期:1981-12-01 00:00:00
abstract::A total of 636 vancomycin-resistant Enterococcus faecium (VRE) isolates that had been obtained between 1994 and 1999 from the Medical School Hospital of the University of Michigan, Ann Arbor, were tested for bacteriocin production. Two hundred seventy-seven (44%) of the strains were bacteriocinogenic; and 193 of these...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1202-1212.2006
更新日期:2006-04-01 00:00:00
abstract::This work investigated the molecular events driving the evolution of the CTX-M-type β-lactamases by the use of DNA shuffling of fragments of the blaCTX-M-14 and blaCTX-M-15 genes. Analysis of a total of 51 hybrid enzymes showed that enzymatic activity could be maintained in most cases, yet hybrids that were active pos...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00891-17
更新日期:2017-11-22 00:00:00
abstract::Although fluoroquinolone antibiotics such as ciprofloxacin are able to gain access to lung tissue and both pleural and bronchial secretions, the characteristics of transport and cellular uptake of ciprofloxacin in human epithelial lung tissue remain obscure. We have chosen human airway epithelial (Calu-3) cells, recon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.12.2693
更新日期:1997-12-01 00:00:00
abstract::The release of inflammatory bacterial products, such as lipopolysaccharide (LPS)/endotoxin, may be increased upon the administration of antibiotics. An improved quantitative understanding of endotoxin release and its relation to antibiotic exposure and bacterial growth/killing may be gained by an integrated analysis o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02070-19
更新日期:2020-03-24 00:00:00
abstract::The in vitro activity of rosamicin and erythromycin was compared at various pH values against 311 strains of bacteria representing common urinary tract pathogens. Alkalinization of the media consistently and significantly increased the antibacterial activity of rosamicin against all of the organisms tested. This was a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.16.1.69
更新日期:1979-07-01 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::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::Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.407-413.2006
更新日期:2006-02-01 00:00:00
abstract::The radical-based theory proposes that three major classes of bactericidal antibiotics, i.e., β-lactams, quinolones, and aminoglycosides, have in common the downstream formation of lethal levels of reactive oxygen species (ROS) as part of the killing mechanism. If bactericidal antibiotics exhibit a common mechanism, t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02354-17
更新日期:2018-05-25 00:00:00
abstract::Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01422-13
更新日期:2014-01-01 00:00:00
abstract::The in vitro activities of ACH-702 and other antimicrobials against 30 Nocardia brasiliensis isolates were tested. The MIC(50) (MIC for 50% of the strains tested) and MIC(90) values of ACH-702 were 0.125 and 0.5 microg/ml. The same values for econazole were 2 and 4 microg/ml. The MIC(50) and MIC(90) values of imipenem...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01520-09
更新日期:2010-05-01 00:00:00
abstract::MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.7.1894-1899.2000
更新日期:2000-07-01 00:00:00