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  • 1
    Online Resource
    Online Resource
    Ceftolozane-Tazobactam in the Treatment of Experimental Pseudomonas aeruginosa Pneumonia in Persistently Neutropenic Rabbits: Impact on Strains with Genetically Defined Mechanisms of Resistance
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 9 ( 2019-09)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 9 ( 2019-09)
    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 ≥10 5 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.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00344-19
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    First Report of bla VIM-4 - and mcr-9 -Coharboring Enterobacter Species Isolated from a Pediatric Patient
    American Society for Microbiology ; 2019
    In:  mSphere Vol. 4, No. 5 ( 2019-10-30)
    Details
    In: mSphere, American Society for Microbiology, Vol. 4, No. 5 ( 2019-10-30)
    Abstract: An Enterobacter hormaechei isolate harboring bla VIM-4 and mcr-9 was recovered from a pediatric patient in a U.S. hospital. The bla VIM-4 and mcr-9 genes are carried on the same IncH12 plasmid, pME-1a. The isolate tested susceptible to colistin, without observed induction of colistin resistance. The mcr-9 gene is located between two insertion elements, IS 903 and IS 1 , but lacks the downstream regulatory genes ( qseC and qseB ) found in other isolates that harbor mcr-9 . IMPORTANCE We describe the complete genome assembly and sequence of a clinical Enterobacter isolate harboring both bla VIM-4 and mcr-9 recovered from a pediatric patient in the United States with a history of travel to Egypt. Moreover, to the best of our knowledge, this is the first report of an Enterobacter isolate harboring both bla VIM-4 and mcr-9 from the United States. The bla VIM-4 and mcr-9 genes are carried on the same IncH12 plasmid, pME-1a. The isolate tested susceptible to colistin, without observed induction of colistin resistance. The mcr-9 gene is located between two insertion elements, IS 903 and IS 1 , but lacks the downstream regulatory genes ( qseC and qseB ) found in other isolates that harbor mcr-9 .
    Type of Medium: Online Resource
    ISSN: 2379-5042
    URL: Article
    DOI: 10.1128/mSphere.00629-19
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 2844248-9
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  • 3
    Online Resource
    Online Resource
    Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine
    American Society for Microbiology ; 2011
    In:  Antimicrobial Agents and Chemotherapy Vol. 55, No. 12 ( 2011-12), p. 5893-5899
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 55, No. 12 ( 2011-12), p. 5893-5899
    Abstract: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause of health care-associated urinary tract infections. Antimicrobials with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort ( n = 41), compared to 64% in the polymyxin B ( P = 0.02; n = 25), 43% in the tigecycline ( P 〈 0.001; n = 21), and 36% in the untreated ( P 〈 0.001; n = 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10; P = 0.003), tigecycline (OR, 0.08; P = 0.001), and untreated (OR, 0.14; P = 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro , was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00387-11
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Efficacy of Cefiderocol in Experimental Stenotrophomonas maltophilia Pneumonia in Persistently Neutropenic Rabbits
    American Society for Microbiology ; 2022
    In:  Antimicrobial Agents and Chemotherapy Vol. 66, No. 10 ( 2022-10-18)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 10 ( 2022-10-18)
    Abstract: Stenotrophomonas maltophilia is an important cause of pneumonia in immunocompromised patients. Cefiderocol is a parenteral siderophore cephalosporin with potent in vitro activity against S. maltophilia . We evaluated the efficacy of cefiderocol in a neutropenic rabbit model of S. maltophilia pneumonia in comparison to trimethoprim-sulfamethoxazole (TMP-SMX). The cefiderocol area under the plasma drug concentration-time curve extrapolated to 8 h (AUC 0–8 ) was lower (423.0 ± 40.9 μg·h/mL versus 713.6 ± 40.1 μg·h/mL) and clearance higher (252.77 ± 38.9 mL/h/kg versus 142.6 ± 32.9 mL/h/kg) in infected versus noninfected rabbits. We studied a clinical bloodstream S. maltophilia isolate with an MIC of 0.03 μg/mL of cefiderocol. Time spent above the MIC of cefiderocol for the majority of S. maltophilia isolates in rabbits recapitulated the plasma concentration-time profile observed in adult humans at the licensed dose of 2 g given intravenously (i.v.). Experimental groups consisted of 120 mg/kg cefiderocol i.v. every 8 hours (q8h); TMP-SMX, 5 mg/kg i.v. Q12h, and untreated controls (UCs). Treatment was administered for 10 days. Survival in cefiderocol-treated rabbits (87%) was greater than that in TMP-SMX-treated (25%; P  〈   0.05) and UC (0%; P  〈   0.05) groups. There was no residual bacterial burden in lung tissue or bronchoalveolar lavage (BAL) fluid in the cefiderocol group. Residual bacterial burden was present in lung tissue and BAL fluid in the TMP-SMX group but was decreased in comparison to UCs ( P  〈   0.001). Lung weights (markers of pulmonary injury) were decreased in cefiderocol-treated versus TMP-SMX ( P   〈  0.001) and UC ( P  〈   0.001) groups. Cefiderocol is highly active in treatment of experimental S. maltophilia pneumonia, laying the foundation for future clinical investigations against this lethal infection in immunocompromised patients.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.00618-22
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
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