Abstract:
:When growing bacteria are exposed to bactericidal concentrations of antibiotics, the sensitivity of the bacteria to the antibiotic commonly decreases with time, and substantial fractions of the bacteria survive. Using Escherichia coli CAB1 and antibiotics of five different classes (ampicillin, ciprofloxacin, rifampin, streptomycin, and tetracycline), we examine the details of this phenomenon and, with the aid of mathematical models, develop and explore the properties and predictions of three hypotheses that can account for this phenomenon: (i) antibiotic decay, (ii) inherited resistance, and (iii) phenotypic tolerance. Our experiments cause us to reject the first two hypotheses and provide evidence that this phenomenon can be accounted for by the antibiotic-mediated enrichment of subpopulations physiologically tolerant to but genetically susceptible to these antibiotics, phenotypic tolerance. We demonstrate that tolerant subpopulations generated by exposure to one concentration of an antibiotic are also tolerant to higher concentrations of the same antibiotic and can be tolerant to antibiotics of the other four types. Using a mathematical model, we explore the effects of phenotypic tolerance to the microbiological outcome of antibiotic treatment and demonstrate, a priori, that it can have a profound effect on the rate of clearance of the bacteria and under some conditions can prevent clearance that would be achieved in the absence of tolerance.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Wiuff C,Zappala RM,Regoes RR,Garner KN,Baquero F,Levin BRdoi
10.1128/AAC.49.4.1483-1494.2005subject
Has Abstractpub_date
2005-04-01 00:00:00pages
1483-94issue
4eissn
0066-4804issn
1098-6596pii
49/4/1483journal_volume
49pub_type
杂志文章abstract::Candida parapsilosis has emerged as a common cause of invasive fungal infection, especially in Latin America and in the neonatal setting. C. parapsilosis is part of a closely related group of organisms that includes the species Candida orthopsilosis and Candida metapsilosis. All three species show elevated MICs for th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00262-08
更新日期:2008-07-01 00:00:00
abstract::In 24 patients with hepatitic C virus (HCV) infection who participated in a randomized trial with alpha 2B interferon, HCV RNA analysis by the polymerase chain reaction with two separate primer sets was performed at weeks 0, 4, and 24 and during a follow-up period of 6 to 9 months. Prior to therapy all patients were H...
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.37.3.595
更新日期:1993-03-01 00:00:00
abstract::Rifampin was shown in vitro to decrease the amphotericin B minimal inhibitory concentrations of all of 10 strains of Coccidioides immitis tested. These decreases ranged from two- to fourfold and occurred with rifampin concentrations of 10 to 40 mug/ml. Rifampin alone was without effect. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.6.783
更新日期:1974-12-01 00:00:00
abstract::Dientamoeba fragilis is a commonly encountered trichomonad which has been implicated as a cause of gastrointestinal disease in humans. Despite the frequency of reports recording infections with this parasite, little research has been undertaken in terms of antimicrobial susceptibility. The aim of this study was to eva...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05125-11
更新日期:2012-01-01 00:00:00
abstract::Monophenol monooxygenase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase EC 1.14.18.1) was studied in melanin-positive and melanin-negative mutants of Streptomyces lincolnensis NCIB 9413, varying in the lincomycin synthesizing ability. The activities of laccase and tyrosine phenol lyase (EC 4.1.99.2) are abs...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.5.526
更新日期:1975-11-01 00:00:00
abstract::Candida albicans biofilms are generally considered to be resistant to azole antifungal agents but susceptible to echinocandins. We demonstrate that in a sequential therapy regimen, treatment with fluconazole first followed by caspofungin leads to a significant decrease of the efficacy of this echinocandin. Cellular st...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01745-13
更新日期:2014-01-01 00:00:00
abstract::Eltrombopag is an orally bioavailable thrombopoietin receptor agonist approved for the treatment of thrombocytopenia associated with chronic immune (idiopathic) thrombocytopenic purpura and chronic hepatitis C virus (HCV) infection. This study evaluated the potential drug-drug interactions between eltrombopag and the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.03091-14
更新日期:2014-11-01 00:00:00
abstract::Violacein is a violet pigment extracted from the gram-negative bacterium Chromobacterium violaceum. It presents bactericidal, tumoricidal, trypanocidal, and antileishmanial activities. We show that micromolar concentrations efficiently killed chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro;...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00693-08
更新日期:2009-05-01 00:00:00
abstract::A prospective study was performed with 23 Helicobacter pylori-infected children (mean age, 9.5 +/- 4.4 years) with clinical symptoms of gastritis and positive results of culture and histologic examination of gastric biopsy specimens to evaluate the influence of antibiotic resistance on eradication. Positive children w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.6.1334
更新日期:1998-06-01 00:00:00
abstract::beta-L-2',3'-Dideoxy-5-fluorocytidine (beta-L-FddC), a novel cytidine analog with an unnatural beta-L sugar configuration, has been demonstrated by our group and others to exhibit highly selective in vitro activity against human immunodeficiency virus types 1 and 2 and hepatitis B virus. This encouraging in vitro anti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.4.920
更新日期:1999-04-01 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::Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin B complexed with the lipids L-alpha-dimyristoylphosphatidylcholine (DMPC) and L-alpha-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Acti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.4.767
更新日期:1998-04-01 00:00:00
abstract::VT-1129 is a novel fungal enzyme-specific Cyp51 inhibitor with potent cryptococcal activity. Because of its long half-life (>6 days in mice) and our desire to quickly reach potent efficacy, we evaluated a VT-1129 loading dose-maintenance dose strategy against cryptococcal meningitis. VT-1129 plasma and brain pharmacok...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01315-18
更新日期:2018-10-24 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::Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited setting...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00439-16
更新日期:2016-09-23 00:00:00
abstract::Nephrotoxicity was more marked in rats receiving isepamicin at midlight than at middark. And, the once-daily administration at middark induced a lesser degree of nephrotoxicity than the twice-daily injection, which indicates that the once-daily treatment therapy may have potential value in the clinical use of aminogly...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.9.2042
更新日期:1993-09-01 00:00:00
abstract::The enterococcal peptide AS-48 exerts a concentration-dependent bactericidal effect on Enterococcus faecalis subsp. liquefaciens S-47; cell rescue by cardiolipin and trypsin can be effected only in the first few minutes after antibiotic addition. Gramicidin-exposed cells are protected from killing by AS-48. Long-term ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.5.641
更新日期:1989-05-01 00:00:00
abstract::Protoplasts of the temperature-sensitive osmotic-1 mutant of Neurospora crassa grew and divided as cell wall-less cells when incubated under certain conditions at 37 degrees C. Each protoplast regenerated cell wall and formed a mycelium when the temperature was shifted to 22 degrees C. Cell wall regeneration, but not ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.5.757
更新日期:1983-05-01 00:00:00
abstract::The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.6.1520
更新日期:1996-06-01 00:00:00
abstract::Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antituss...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00950-10
更新日期:2011-03-01 00:00:00
abstract::A wide variety of prokaryotic and eukaryotic cells exhibit a multidrug resistance (MDR) phenotype, indicating that resistance to potentially toxic compounds is mediated by their active efflux from the cell. We have sought to determine whether resistance to azoles in some strains of Candida species may be due in part t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.2.419
更新日期:1996-02-01 00:00:00
abstract::To study the antimalarial action of chloroquine, normal mouse erythrocytes were used as surrogates for erythrocytoid bodies. These bodies form in the endosomes of intraerythrocytic malaria parasites as they feed on their host and consist of erythrocyte cytoplasm enclosed in a vestige of the erythrocyte membrane. In su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01652-05
更新日期:2006-07-01 00:00:00
abstract::Upregulated expression of efflux pumps, lpxC target mutations, LpxC protein overexpression, and mutations in fabG were previously shown to mediate single-step resistance to the LpxC inhibitor CHIR-090 in P. aeruginosa Single-step selection experiments using three recently described LpxC inhibitors (compounds 2, 3, and...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01490-19
更新日期:2019-12-20 00:00:00
abstract::Yersinia enterocolitica has emerged as an enteropathogen associated with several types of human infections that often require antimicrobial therapy, but little is known about the antimicrobial susceptibilities of pathogenic strains isolated from humans in Canada. To determine the present patterns of antimicrobial susc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2121
更新日期:1994-09-01 00:00:00
abstract::Exposure-response analyses for efficacy and safety were performed for tigecycline-treated patients suffering from community-acquired pneumonia. Data were collected from two randomized, controlled clinical trials in which patients were administered a 100-mg loading dose followed by 50 mg of tigecycline every 12 h. A ca...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00277-10
更新日期:2012-01-01 00:00:00
abstract::There is concern about the rise of antifungal drug resistance, but little is known about comparative biological properties and pathogenicity of drug-resistant strains. We generated fluconazole (FLC; CO23 RFLC)- or micafungin (FK; CO23 RFK)-resistant strains of Candida albicans by treating a FLC- and FK-susceptible str...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01223-07
更新日期:2008-03-01 00:00:00
abstract::Interpretive agreements among the results of fluconazole broth microdilution tests, Etests, and disk diffusion tests were documented by evaluating 495 Candida spp. Microdilution reference test results were in agreement with 96% of the Etest results; most discrepancies were minor differences. Fluconazole resistance of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.6.1781-1784.2002
更新日期:2002-06-01 00:00:00
abstract::Resistance to ceftazidime, detected in isolates of Escherichia coli 5518 and Enterobacter gergoviae 3773 from our hospital, was transferred, together with resistance to aminoglycosides, trimethoprim, sulfonamide, and other beta-lactam antibiotics, by conjugation to E. coli JP559. Both E. coli transconjugants were resi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.12.2838
更新日期:1994-12-01 00:00:00
abstract::We have previously shown that genetic disruption of Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3) affects calcium ionophore-induced egress. We examined whether Plasmodium falciparum CDPK1 (PfCDPK1), the closest homolog of TgCDPK3 in the malaria parasite P. falciparum, could complement a TgCDPK3 mutant...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02261-13
更新日期:2014-05-01 00:00:00
abstract::Treatment of mucocutaneous and cutaneous Candida albicans infections with photosensitizing agents and light, termed photodynamic therapy (PDT), offers an alternative to conventional treatments. Initial studies using the clinically approved photosensitizer Photofrin demonstrated the susceptibility of C. albicans to its...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.10.4288-4295.2005
更新日期:2005-10-01 00:00:00