Abstract:
:Killing by beta-lactams is well known to be reduced against a dense bacterial population, commonly known as the inoculum effect. However, the underlying mechanism of this phenomenon is not well understood. We proposed a semi-mechanistic mathematical model to account for the reduced in vitro killing observed. Time-kill studies were performed with 4 baseline inocula (ranging from approximately 1 × 10(5) to 1 × 10(8) CFU/ml) of Escherichia coli ATCC 25922 (MIC, 2 mg/liter). Constant but escalating piperacillin concentrations used ranged from 0.25× to 256× MIC. Serial samples were taken over 24 h to quantify viable bacterial burden, and all the killing profiles were mathematically modeled. The inoculum effect was attributed to a reduction of effective drug concentration available for bacterial killing, which was expressed as a function of the baseline inoculum. Biomasses associated with different inocula were examined using a colorimetric method. Despite identical drug-pathogen combinations, the baseline inoculum had a significant impact on bacterial killing. Our proposed mathematical model was unbiased and reasonable in capturing all 28 killing profiles collectively (r(2) = 0.88). Biomass was found to be significantly more after 24 h with a baseline inoculum of 1 × 10(8) CFU/ml, compared to one where the initial inoculum was 1 × 10(5) CFU/ml (P = 0.002). Our results corroborated previous observations that in vitro killing by piperacillin was significantly reduced against a dense bacterial inoculum. This phenomenon can be reasonably captured by our proposed mathematical model, and it may improve prediction of bacterial response to various drug exposures in future investigations.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Bhagunde P,Chang KT,Singh R,Singh V,Garey KW,Nikolaou M,Tam VHdoi
10.1128/AAC.01831-09subject
Has Abstractpub_date
2010-11-01 00:00:00pages
4739-43issue
11eissn
0066-4804issn
1098-6596pii
AAC.01831-09journal_volume
54pub_type
杂志文章abstract::Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even, rarely, mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Covering only first-line antituberculosis drugs, this review addresses whether and how...
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.6.2.117
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.15.6.758
更新日期:1979-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.35.7.1515
更新日期:1991-07-01 00:00:00
abstract::Disk susceptibility tests with two structurally related aminoglycosides (amikacin and Sch 21420) were evaluated. Tests with 10- and 30-micrograms amikacin disks confirmed previous recommendations for interpretive zone standards; 30-micrograms disks are preferred. Tests with 10-, 20-, and 30-micrograms Sch 21420 disks ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.4.616
更新日期:1980-10-01 00:00:00
abstract::The 8-aminoquinoline tafenoquine showed significant in vitro activity against Leishmania species, including L. donovani amastigotes in macrophages, with 50% inhibitory concentrations (IC(50)s) between 0.1 and 4.0 μM for both pentavalent antimony (SbV)-sensitive and SbV-resistant strains and by oral administration in B...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00985-10
更新日期:2010-12-01 00:00:00
abstract::Imipenem-cilastatin concentrations in bile were measured in 12 cholecystectomy patients (group 1) and 12 patients with common duct drainage (group 2). Six patients in each group received 0.5 g, and six received 1.0 g intravenously over 30 to 60 min. In group 1, bile was collected a mean of 85 min postinfusion. The mea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1718
更新日期:1987-11-01 00:00:00
abstract::The new fluoroquinolone trovafloxacin was tested against a ciprofloxacin-sensitive, methicillin-resistant Staphylococcus aureus strain in the rabbit model of endocarditis. Trovafloxacin was more effective than vancomycin (CFU/g of vegetation, 2.65 +/- 1.87 versus 4.54 +/- 2.80 [mean +/- standard deviation]; P < 0.05) ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3325
更新日期:1998-12-01 00:00:00
abstract::A rapid, sensitive, and specific method of analysis for mezlocillin in serum and urine by high-pressure liquid chromatography is described. A solid-phase extraction column was used to remove interfering substances from samples before chromatography. Quantitation included the use of an internal standard, nafcillin. Mez...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.5.775
更新日期:1984-11-01 00:00:00
abstract::Hydrophilic albumin microspheres are proposed as a new delivery system for amphotericin B (AMB; AMB microspheres). The acute toxicity of AMB microspheres was lower than that of the AMB-deoxycholate (AMB-Doc) reference formulation in hamsters. Lethal doses in healthy and infected animals were improved at least eight ti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.4.618
更新日期:1982-04-01 00:00:00
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abstract::In vitro activity of tebipenem, a new oral carbapenem antibiotic, against clinical Haemophilus influenzae isolates was compared with those of 8 reference agents. Isolates were classified into 6 resistance classes after PCR identification of beta-lactamase genes and ftsI gene mutations. For all isolates, the minimal co...
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.1.74
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abstract::Forty-one children <8 years of age treated for brucellosis with oral minocycline (2.5 mg/kg) twice daily for 3 weeks were recalled and examined to check for dental staining and defects. Dental staining and defects were found in 14 of 41 exposed children (34.1%) and in 30 of 82 matched controls (36.6%), respectively (P...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.7.2739-2741.2004
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abstract::Morganocin 174-induced lethality was characterized by one-hit kinetics. Although it induced simultaneous inhibition of deoxyribonucleic acid, ribonucleic acid, and protein syntheses, the most striking effect of morganocin was a rapid reduction of intracellular adenosine 5'-triphosphate to less than 10% of the initial ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.3.395
更新日期:1977-09-01 00:00:00
abstract::Hyperbaric oxygen exposures were evaluated for treatment of progressive liver abscesses produced by intraperitoneal injection of combined cultures of Fusobacterium necrophorum plus either Bacteroides fragilis subsp. fragilis or Fusobacterium nucleatum in a mouse model. Infected control and hyperbaric oxygen-exposed mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.2.312
更新日期:1976-02-01 00:00:00
abstract::Colistin resistance, although uncommon, is increasingly being reported among Gram-negative clinical pathogens, and an understanding of its impact on the activity of antimicrobials is now evolving. We evaluated the potential for synergy of colistin plus trimethoprim, trimethoprim-sulfamethoxazole (1/19 ratio), or vanco...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.11.2006
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abstract::Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
abstract::Burkholderia cepacia complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis p...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2014-09-01 00:00:00
abstract::Recently, strains of Neisseria gonorrhoeae have been isolated which are highly resistant to tetracycline (MICs of 16 to 64 micrograms/ml). This resistance was due to the acquisition of the resistance determinant tetM, a transposon-borne determinant initially found in the genus Streptococcus and more recently in Mycopl...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1986-11-01 00:00:00