Abstract:
:Arguably, one of the most common and consequential laboratory tests performed in the world is Mycobacterium tuberculosis susceptibility testing. M. tuberculosis resistance is defined by growth of > or =1% of a bacillary inoculum on the critical concentration of an antibiotic. The critical concentration was chosen based on inhibition of > or =95% of wild-type isolates. The critical concentration of isoniazid is either 0.2 or 1.0 mg/liter, that of rifampin is 1.0 mg/liter, that of pyrazinamide is 100 mg/liter, that of ethambutol is 5.0 mg/liter, and that of fluoroquinolones is 1.0 mg/liter. However, the relevance of these concentrations to microbiologic and clinical outcomes is unclear. Critical concentrations were identified using the ability to achieve the antibiotic area under the concentration-time curve/MIC ratio associated with > or =90% of maximal kill (EC(90)) of M. tuberculosis in > or =90% of patients. Population pharmacokinetic parameters and their variability encountered in tuberculosis patients were utilized in Monte Carlo simulations to determine the probability that particular daily doses of the drugs would achieve or exceed the EC(90) in the epithelial lining fluid of 10,000 tuberculosis patients. Failure to achieve EC(90) in > or =90% of patients at a particular MIC was defined as drug resistance. The critical concentrations of moxifloxacin and ethambutol remained unchanged, but a critical concentration of 50 mg/liter was identified for pyrazinamide, 0.0312 mg/liter and 0.125 mg/liter were defined for low- and high-level isoniazid resistance, respectively, and 0.0625 mg/liter was defined for rifampin. Thus, current critical concentrations of first-line antituberculosis drugs are overoptimistic and should be set lower. With the proposed breakpoints, the rates of multidrug-resistant tuberculosis could become 4-fold higher than currently assumed.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Gumbo Tdoi
10.1128/AAC.01474-09subject
Has Abstractpub_date
2010-04-01 00:00:00pages
1484-91issue
4eissn
0066-4804issn
1098-6596pii
AAC.01474-09journal_volume
54pub_type
杂志文章abstract::Cytochrome aa3 concentrations in the cytoplasmic membrane of Bacillus subtilis were altered by growth conditions, and the effects on the membrane potential (delta psi) in whole cells were measured. When cytochrome aa3 was absent, the magnitude of delta psi was not diminished by comparison with the delta psi measured i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.1.141
更新日期:1986-01-01 00:00:00
abstract::In patients with polytrauma or major surgery, severe bacterial infections leading to septic shock and multiorgan failure are still a major cause of death. Prevention of septic shock in patients at risk would be an alternative to treatment of patients with overt septic shock. We therefore conducted a trial with the mon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.11.2535
更新日期:1995-11-01 00:00:00
abstract::Mycobacterium smegmatis DSM43756 inactivates rifampin, and the inactivated antibiotic product recovered from culture medium was ribosylated on the 23-OH group. To study this process, the gene responsible for the inactivation was expressed at high levels by the lac promoter in Escherichia coli conferring resistance to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.1.181
更新日期:1999-01-01 00:00:00
abstract::A cluster of genes involved in antibiotic and heavy metal resistance has been characterized from a clinical isolate of the gram-negative bacterium Stenotrophomonas maltophilia. These genes include a macrolide phosphotransferase (mphBM) and a cadmium efflux determinant (cadA), together with the gene cadC coding for its...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.7.1778-1782.2000
更新日期:2000-07-01 00:00:00
abstract::The racemic nucleoside analogue 2'-deoxy-3'-oxa-4'-thiocytidine (dOTC) is in clinical development for the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection. dOTC is structurally related to lamivudine (3TC), but the oxygen and sulfur in the furanosyl ring are transposed. Intracellular metabolism ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.8.1835
更新日期:1999-08-01 00:00:00
abstract::Levels of roxithromycin in serum and tissue were investigated in 29 subjects undergoing tonsillectomy. A total of 13 subjects received a single oral dose of 300 mg, and 16 received four oral doses 12 h apart as follows: a 300-mg loading dose followed by three 150-mg doses. Measurable levels of roxithromycin were prese...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.9.1461
更新日期:1988-09-01 00:00:00
abstract::We reported previously that intraperitoneal administration of a bis(benzyl)polyamine analog, MDL 27,695, suppressed both pentavalent antimony (Sbv)-susceptible and -resistant Leishmania donovani in vivo. The present studies were performed to optimize parasite suppression by parenteral administration and to evaluate th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.7.1403
更新日期:1991-07-01 00:00:00
abstract::Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC in a patient cohort to identify the causative organisms associated with VVC. Biofilm-forming capacity and antifungal sensitivity profiles were also assessed. We re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01065-17
更新日期:2017-08-24 00:00:00
abstract::Viral infections are among the main causes of death worldwide, and we lack antivirals for the majority of viruses. Heparin-like sulfated or sulfonated compounds have been known for decades for their ability to prevent infection by heparan sulfate proteoglycan (HSPG)-dependent viruses but only in a reversible way. We h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02001-20
更新日期:2020-11-17 00:00:00
abstract::The biliary excretion of moxalactam was studied in 11 postsurgery patients who had indwelling T-tubes inserted in their common bile ducts. Peak levels of moxalactam in the bile reached mean levels of 33.7 +/- 11.1 and 173.7 +/- 67.0 micrograms/ml 2 h after intravenous administration of a single 500- or 2,000-mg dose, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.2.231
更新日期:1981-08-01 00:00:00
abstract::Many gram-negative bacteria are known to be remarkably resistant to hydrophobic noxious agents by virtue of their outer membranes (OM). We investigated, by using four different assay methods, the ability of sodium hexametaphosphate (HMP) to disrupt this OM barrier. (i) In the growth inhibition assay, HMP was found to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.10.1741
更新日期:1989-10-01 00:00:00
abstract::Seventy-five strains of Haemophilus influenzae type b, including 45 beta-lactamase-positive strains, were tested by MIC and time kill studies for susceptibility to ampicillin-sulbactam at various ratios. beta-Lactamase-negative strains were inhibited by lower concentrations of ampicillin-sulbactam than beta-lactamase-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1620
更新日期:1989-09-01 00:00:00
abstract::A study was performed to determine the effect of parenteral treatment with four broad-spectrum cephalosporins (cefoperazone, ceftriaxone, ceftazidime, and cefepime) on the number of aerobic gram-negative rods and on the outgrowth of Candida albicans and a multiresistant strain of Citrobacter freundii in the feces of m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.5.976
更新日期:1991-05-01 00:00:00
abstract::Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survival in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.5.1127
更新日期:1995-05-01 00:00:00
abstract::The in vitro inhibitory effects of quinolones on the bacterial DNA gyrase of Escherichia coli KL-16 and topoisomerase II of fetal calf thymus were compared. All the quinolones tested required higher concentrations to inhibit the topoisomerase II than to inhibit the DNA gyrase, and no correlation existed among their in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.10.1816
更新日期:1989-10-01 00:00:00
abstract::Mannopeptimycins alpha, beta, gamma, delta, and epsilon are new cyclic glycopeptide antibiotics produced by Streptomyces hygroscopicus LL-AC98. Mannopeptimycins gamma, delta, and epsilon, which have an isovaleryl substitution at various positions on the terminal mannose of the disaccharide moiety, demonstrated moderat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.1.62-69.2003
更新日期:2003-01-01 00:00:00
abstract::The susceptibilities of 430 Campylobacter jejuni strains and 79 C. coli strains to six antimicrobial agents were tested and analyzed. The two sets of strains originated from retail market chicken and turkey samples and from humans, respectively, in Berlin, Germany. Two groups of isolates, one dating from 1991 and the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.12.3825-3830.2003
更新日期:2003-12-01 00:00:00
abstract::The increasing incidence and severity of infection by Clostridium difficile have stimulated attempts to develop new antimicrobial therapies. We report here the relative abilities of two antibiotics (metronidazole and vancomycin) in current use for treating C. difficile infection and of a third antimicrobial, surotomyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00275-15
更新日期:2015-07-01 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::In 2016, we identified a new class A carbapenemase, VCC-1, in a nontoxigenic Vibrio cholerae strain that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1-producing V. cholerae isolates were recovered along the German coastline. These isolates a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02112-18
更新日期:2019-03-27 00:00:00
abstract::In both primary rabbit kidney cells and human skin fibroblasts, 5-propyl-2'-deoxyuridine proved inhibitory to herpes simplex virus at a concentration as low as 1 micrograms/ml, whereas concentrations higher than 200 micrograms/ml were required to inhibit vaccinia virus replication or normal cell metabolism. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.3.545
更新日期:1978-03-01 00:00:00
abstract::Of the 176 randomly selected, commensal, gram-negative bacteria isolated from healthy children with low exposure to antibiotics, 138 (78%) carried one or more of the seven macrolide resistance genes tested in this study. These isolates included 79 (91%) isolates from the oral cavity and 59 (66%) isolates from urine sa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3451-3456.2004
更新日期:2004-09-01 00:00:00
abstract::The susceptibilities to 20 antimicrobial agents of Bordetella bronchiseptica variants in C mode and degraded phases were compared with those of their parents in X mode. Increases in MICs of 4- to 32-fold were observed for ampicillin, carbenicillin, erythromycin, novobiocin, rifampin, chloramphenicol, nalidixic acid, a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.12.1891
更新日期:1988-12-01 00:00:00
abstract::The in vitro activities of GAR-936, the 9-t-butylglycylamido derivative of minocycline, were compared with those of doxycycline, minocycline, and tetracycline against 527 gram-positive clinical isolates. GAR-936 inhibited all strains, including those resistant to other tetracyclines, at concentrations of =2 microg/m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.8.2225-2229.2000
更新日期:2000-08-01 00:00:00
abstract::Multiresistant enterococci were tested for susceptibility to trimethoprim (TMP). Although most enterococci are inhibited by less than or equal to 1.0 microgram/ml, the MICs for 7 of 29 selected multiresistant isolates were greater than or equal to 8 micrograms/ml, including for two beta-lactamase positive (Bla+) strai...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.9.1928
更新日期:1991-09-01 00:00:00
abstract::Due to the rise of antibiotic resistance and the small number of effective antiviral drugs, new approaches for treating infectious diseases are urgently needed. Identifying targets for host-based therapies represents an emerging strategy for drug discovery. The ubiquitin-proteasome system is a central mode of signalin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03021-15
更新日期:2016-06-20 00:00:00
abstract::The caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3616-3623.2005
更新日期:2005-09-01 00:00:00
abstract::PD 131628 is a new aminopyrrolidine-substituted fluorocyclopropyl naphthyridine quinolone which possesses high in vitro activity against a wide spectrum of bacterial species. The MICs for greater than or equal to 90% of strains were 0.125 to 0.25 microgram/ml for staphylococci, Streptococcus pyogenes, and S. pneumonia...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.1.141
更新日期:1991-01-01 00:00:00
abstract::Pseudomonas aeruginosa is equipped with the Sec and Tat protein secretion systems, which translocate the xenobiotic transporter MexAB-OprM and the pathogenic factor phospholipase C (PlcH), respectively. When the signal sequence of MexA was replaced with that of PlcH, the hybrid protein was successfully expressed and r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01495-09
更新日期:2010-04-01 00:00:00
abstract::A membrane fraction from Pseudomonas aeruginosa KM 338 was shown to catalyze in vitro peptidoglycan synthesis from uridine 5'-diphosphate-N-acetylmuramyl-l-alanyl-d- glutamyl-meso-diaminopimelyl-d-alanyl-d-alanine and uridine 5'-diphosphate-N-acetylglucosamine. Synthesized peptidoglycan was partially cross-linked by t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.6.672
更新日期:1974-12-01 00:00:00