Abstract:
:Ceftolozane-tazobactam (C/T) is a novel cephalosporin with in vitro activity against Pseudomonas aeruginosa that is resistant to extended-spectrum penicillins and antipseudomonal cephalosporins. In order to assess the antimicrobial effect of C/T in treatment of Pseudomonas pneumonia, we investigated the pharmacokinetics and efficacy of C/T in persistently neutropenic rabbits. Pseudomonas pneumonia was established by direct endotracheal inoculation. Treatment groups consisted of C/T, ceftazidime (CAZ), piperacillin-tazobactam (TZP), and untreated controls (UC). Rabbits received a dosage of C/T of 80 mg/kg every 4 h (q4h) intravenously (i.v.) (53 mg/kg ceftolozane/26 mg/kg tazobactam) to match the free drug time above the MIC as well as a comparable plasma area under the concentration-time curve (AUC) (humanized doses of ceftolozane-tazobactam of 3 g [2 g/1 g]) q8h, due to the more rapid elimination of ceftolozane in rabbits (0.75 h) than in humans (2.5 h). Four molecularly characterized clinical P. aeruginosa isolates from patients with pneumonia were studied, including one isolate from each classification group: pan-susceptible (PS), outer membrane porin D (OPRD) porin loss (OPRDPL), efflux pump expression (EPE), and AmpC hyperexpression (ACHE). Treatment was continued for 12 days. Treatment with ceftolozane-tazobactam resulted in a ≥105 reduction in residual pulmonary and bronchoalveolar lavage (BAL) fluid bacterial burdens caused by all 4 strains (P ≤ 0.01). This antibacterial activity coincided with reduction of lung weight (an organism-mediated pulmonary injury marker) (P < 0.05). CAZ was less active in ACHE-infected rabbits, and TZP had less activity against EPE, ACHE, and OPRDPL strains. Survival was prolonged in the C/T and CAZ treatment groups in comparison to the TZP and UC groups (P < 0.001). Ceftolozane-tazobactam is highly active in treatment of experimental P. aeruginosa pneumonia in persistently neutropenic rabbits, including infections caused by strains with the most common resistance mechanisms.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Petraitis V,Petraitiene R,Naing E,Aung T,Thi WP,Kavaliauskas P,Win Maung BB,Michel AO,Ricart Arbona RJ,DeRyke AC,Culshaw DL,Nicolau DP,Satlin MJ,Walsh TJdoi
10.1128/AAC.00344-19subject
Has Abstractpub_date
2019-08-23 00:00:00issue
9eissn
0066-4804issn
1098-6596pii
AAC.00344-19journal_volume
63pub_type
杂志文章abstract::BMS-207147, Sch 56592, and voriconazole are three new investigational triazoles with broad-spectrum antifungal activity. The in vitro activities of these three agents were compared with those of itraconazole and fluconazole against 1,300 bloodstream isolates of Candida species obtained from over 50 different medical c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3242
更新日期:1998-12-01 00:00:00
abstract::Two new fluorinated oxazolidinones, U-100592 and U-100766, were evaluated against more than 659 gram-positive and -negative organisms and compared with glycopeptides, erythromycin, clindamycin, clinafloxacin, and chloramphenicol. U-100592 and U-100766 were usually equally potent, but the MICs at which 90% of the isola...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.3.720
更新日期:1996-03-01 00:00:00
abstract::Thirty-five strains of Pasteurella multocida from humans and animals were tested for susceptibility to five cephalosporins by a broth dilution method. Cefcanel showed high activity against all isolates (MIC and MBC, less than or equal to 0.64 micrograms/ml). The corresponding figure for cefaclor and cefuroxime was 2.5...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.12.2142
更新日期:1989-12-01 00:00:00
abstract::The rapid infusion of hyperosmolar solutions into the internal carotid artery transiently disrupts the integrity of the blood-brain barrier, permitting entry of substances normally excluded from the nervous system. This study examined the effect of such an infusion on the penetration of vancomycin and tobramycin into ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.3.339
更新日期:1983-09-01 00:00:00
abstract::We previously showed that simian immunodeficiency virus-infected macaque macrophages contacting uninfected CD4+ lymphocytes caused extensive cell fusion and synthesis of phlogistic cytokines. In this study, macaque macrophage cultures inoculated with SIVmac251 and treated simultaneously with 10 microM 3'-azidothymidin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.360
更新日期:1993-02-01 00:00:00
abstract::Mutants of Escherichia coli K-12 that are unable to make use of the enterochelin transport system were used to confirm that streptonigrin requires iron for its bactericidal action. Correlation of viability studies and 55Fe3+ uptake experiments showed that killing by streptonigrin increased with an increase in 55Fe3+ u...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.6.961
更新日期:1982-12-01 00:00:00
abstract::We studied the DNA sequence variation of van genes of 34 isolates of Enterococcus spp. The isolates containing the vanB gene exhibited between 0 and 41 base pair changes per 801 bp studied when the vanB sequences were compared to that of the reference strain Enterococcus faecalis V583. The isolates carrying the vanC-2...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.1.202
更新日期:1998-01-01 00:00:00
abstract::Desbutyl-benflumetol (DBB) is a novel antimalarial compound closely related to benflumetol (lumefantrine), of which it is a putative metabolite. The in vitro response of Plasmodium falciparum to DBB was studied in Mae Hong Son and Mae Sot, in northwest Thailand, in 1997 and 1998. In total, 155 fresh isolates were succ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.7.2106-2109.2001
更新日期:2001-07-01 00:00:00
abstract::Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00509-12
更新日期:2012-08-01 00:00:00
abstract::Cationic antimicrobial peptides (CAPs) play important roles in host immune defenses. Plectasin is a defensin-like CAP isolated from the saprophytic fungus Pseudoplectania nigrella. NZ2114 is a novel variant of plectasin with potent activity against Gram-positive bacteria. In this study, we investigated (i) the in vivo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00453-11
更新日期:2011-11-01 00:00:00
abstract::Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.298
更新日期:1981-09-01 00:00:00
abstract::Bacterial pathogens have specific virulence factors (e.g., toxins) that contribute significantly to the virulence and infectivity of microorganisms within the human hosts. Virulence factors are molecules expressed by pathogens that enable colonization, immunoevasion, and immunosuppression, obtaining nutrients from the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01945-12
更新日期:2013-02-01 00:00:00
abstract::Carbapenem pharmacokinetic (PK) profiles are significantly different in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases, and the majority of these studies had small sample sizes. The aim of th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00385-20
更新日期:2020-05-21 00:00:00
abstract::Seventy-two (54.5%) out of 132 fecal samples from a group of yellow-legged gulls in Barcelona, Spain, were positive for Escherichia coli producing either extended-spectrum β-lactamases (ESBL) (51.5%), carbapenemase (1.5%), or cephamycinase (1.5%). The isolation of two carbapenemase-producing E. coli strains is a matte...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02071-16
更新日期:2017-01-24 00:00:00
abstract::Salmonella enterica serovar Typhi is an important pathogen exclusively for humans and causes typhoid or enteric fever. It has been shown that type IVB pili, encoded by the S. enterica serovar Typhi pil operon located in Salmonella pathogenicity island 7, are important in the pathogenic process. In this study, by using...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.10.4052-4060.2005
更新日期:2005-10-01 00:00:00
abstract::Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00389-17
更新日期:2017-07-25 00:00:00
abstract::At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadrox...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.2.331
更新日期:1977-02-01 00:00:00
abstract::We studied the efficacy of pentamidine (PNT) as prophylaxis or early treatment in acute pulmonary fusariosis in neutropenic mice. PNT-preexposed mice had significantly improved survival and reduced fungal burden compared to amphotericin B-preexposed and untreated mice. PNT-treated mice had increased survival but no di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.1.294-297.2006
更新日期:2006-01-01 00:00:00
abstract::Norfloxacin is a quinolone (pyridonecarboxylic acid derivative) effective against Pseudomonas aeruginosa infections. We studied the effects of this drug on DNA metabolism in P. aeruginosa. Norfloxacin inhibits DNA replication immediately on its addition to a logarithmically growing culture of P. aeruginosa. It inhibit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.1.1
更新日期:1986-01-01 00:00:00
abstract::Mecillinam is an amidino penicillinate derivative with a broad spectrum of activity against many gram-negative bacilli. Moreover, marked in vitro synergy against these organisms occurs when mecillinam is combined with other beta-lactam antibiotics. The purpose of this study was to determine the pharmacokinetic disposi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.6.952
更新日期:1980-12-01 00:00:00
abstract::Current data indicate that once-daily aminoglycoside therapy is as efficacious as traditional multiple daily dosing and equally or less toxic. Our experience with once-daily gentamicin, 6 mg/kg of body weight led to a 10% (3 of 33 patients) occurrence of documented ototoxicity after prolonged aminoglycoside exposure. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.2209
更新日期:1996-09-01 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 present study was designed to determine the temporal changes in tobramycin nephrotoxicity during the dark and the light periods of the day and to look for the mechanisms of such changes. Female Sprague-Dawley rats (9 to 11 weeks old) were housed in a 14-h-light-10-h-dark cycle (lights on 0600 to 2000 h). A bolus o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.1.54
更新日期:1994-01-01 00:00:00
abstract::GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low k(cat) values for carbapenems. Twenty-two GES variants have been discovered thus far, di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01272-12
更新日期:2012-11-01 00:00:00
abstract::To study whether the capability of horizontal DNA transfer is associated with metronidazole resistance in Helicobacter pylori, a total of 81 clinical isolates were tested for MICs of metronidazole (MTZ). The MIC assays were performed by using the E-test and reconfirmed by the agar dilution method. Natural competence a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.5.1564-1567.2002
更新日期:2002-05-01 00:00:00
abstract::The activity of methacycline against microbial L-forms and their parent bacteria was compared with that of oxytetracycline, chlortetracycline, tetracycline, and demethylchlortetracycline, as well as with that of 22 other antibiotics which included examples of major groups of antibiotics. The L-forms and bacteria used ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.2.4.276
更新日期:1972-10-01 00:00:00
abstract::The in vitro activity of tebipenem (TBM), a new oral carbapenem antibiotic, against Streptococcus pneumoniae clinical isolates (n = 202) was compared with those of 15 reference agents. The isolates were classified into five genotypic classes after PCR identification of abnormal pbp1a, pbp2x, and pbp2b genes: (i) penic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.889-894.2005
更新日期:2005-03-01 00:00:00
abstract::A PCR-based technique using new fluorescent probes, called molecular beacons, was developed to detect the antifolate resistance-associated S108N point mutation in Plasmodium falciparum. One hundred African clinical isolates were tested by the new method in comparison with the PCR-restriction fragment length polymorphi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.12.3461-3464.2000
更新日期:2000-12-01 00:00:00
abstract::Women in the second half of pregnancy, who were infected with genital mycoplasmas and who gave written informed consent, were randomly assigned to receive capsules of identical appearance containing erythromycin estolate, clindamycin hydrochloride, or a placebo for 6 weeks. Levels of serum glutamic oxalacetic transami...
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.12.5.630
更新日期:1977-11-01 00:00:00
abstract::The mechanism of action of the fungicidal peptide auristatin PHE was investigated in Cryptococcus neoformans. Since auristatin PHE causes budding arrest in C. neoformans (T. Woyke, G. R. Pettit, G. Winkelmann, and R. K. Pettit, Antimicrob. Agents Chemother. 45:3580-3584, 2001), microtubule integrity and nuclear locali...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.12.3802-3808.2002
更新日期:2002-12-01 00:00:00