Multicenter surveillance of in vitro activities of cefepime-zidebactam, cefepime-enmetazobactam, omadacycline, eravacycline, and comparator antibiotics against Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex causing bloodstream infection in Taiwan, 2020

ABSTRACTRX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae(657),Pseudomonas aeruginosa(200), andAcinetobacter baumannii(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% ofEnterobacteriaceaeisolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positiveProtea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active againstPseudomonas aeruginosaisolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active againstP. aeruginosathan tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent againstAcinetobacter baumannii(MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.

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Short versus prolonged courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection: a retrospective study

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab358 ◽

2021 ◽

Author(s):

Moonsuk Bae ◽

Yunseo Jeong ◽

Seongman Bae ◽

Min Jae Kim ◽

Yong Pil Chong ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Bloodstream Infection ◽

Antimicrobial Therapy ◽

Antimicrobial Agents ◽

Propensity Score Analysis ◽

Tertiary Care ◽

Care Hospital ◽

Short Course ◽

Significant Difference

Abstract Background The optimal duration of antimicrobial therapy for uncomplicated Pseudomonas aeruginosa bloodstream infection (BSI) is unknown. We compared the outcomes of short and prolonged courses of antimicrobial therapy in adults with uncomplicated pseudomonal BSI. Methods All patients with uncomplicated P. aeruginosa BSI admitted at a tertiary-care hospital from April 2010 to April 2020 were included. We compared the primary outcome (a composite of the rate of recurrent P. aeruginosa infection and mortality within 30 days after discontinuing antimicrobial therapy) among patients who underwent short (7‒11 days) and prolonged (12‒21 days) courses of antimicrobial therapy using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. Results We evaluated 1477 patients with P. aeruginosa BSI; of them, 290 met the eligibility criteria who received antimicrobial agents with in vitro activity, including 97 (33%) who underwent short-course therapy [median of 9 (IQR = 8‒11) days] and 193 (67%) who underwent prolonged-course therapy [median of 15 (IQR = 14‒18) days]. We found no significant difference in the risk of recurrence or 30 day mortality between the prolonged-course and short-course groups [n = 30 (16%) versus n = 11 (11%); IPTW-adjusted HR = 0.68, 95% CI = 0.34 − 1.36, P = 0.28]. The prolonged-course therapy did not significantly reduce the risk of the recurrence of P. aeruginosa infection within 180 days compared with short-course therapy [n = 37 (19%) versus n = 12 (12%); IPTW-adjusted HR = 0.57, 95% CI = 0.29 − 1.10, P = 0.09]. Conclusions Short-course antimicrobial therapy could be as effective as prolonged-course therapy for uncomplicated P. aeruginosa BSI.

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In vitro activity of cefoperazone and cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa

Infection and Drug Resistance ◽

10.2147/idr.s181201 ◽

2018 ◽

Vol Volume 12 ◽

pp. 25-29 ◽

Cited By ~ 5

Author(s):

Chih-Cheng Lai ◽

Chi-Chung Chen ◽

Ying-Chen Lu ◽

Yin-Ching Chuang ◽

Hung-Jen Tang

Keyword(s):

Pseudomonas Aeruginosa ◽

Acinetobacter Baumannii ◽

Vitro Activity ◽

In Vitro Activity ◽

Carbapenem Resistant

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Pharmacodynamics of the Antibacterial Effect of and Emergence of Resistance to Doripenem in Pseudomonas aeruginosa and Acinetobacter baumannii in anIn VitroPharmacokinetic Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.06111-11 ◽

2012 ◽

Vol 56 (10) ◽

pp. 5009-5015 ◽

Cited By ~ 13

Author(s):

Karen E. Bowker ◽

Alan R. Noel ◽

Sharon G. Tomaselli ◽

Heather Elliott ◽

Alasdair P. MacGowan

Keyword(s):

Pseudomonas Aeruginosa ◽

Acinetobacter Baumannii ◽

Exposure Dose ◽

Viable Count ◽

Dose Fractionation ◽

Single Strain ◽

Content Type ◽

Multiple Exposures ◽

Unit Reduction

ABSTRACTAnin vitrodilutional pharmacokinetic model of infection was used to study the pharmacodynamics of doripenem in terms of the ability to killPseudomonas aeruginosaorAcinetobacter baumanniiand also changes in their population profiles. In dose-ranging studies, the cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMICs) required for doripenem to produce a 24-h bacteriostatic effect and a −2-log-unit reduction in viable count were 25% ± 11% and 35% ± 13%, respectively, forP. aeruginosa(MIC range, 0.24 to 3 mg/liter) and 20% ± 11% and 33% ± 12%, respectively, forAcinetobacterspp. (MIC range, 0.45 to 3.0 mg/liter). ATMICof >40 to 50% produced a maximum response with both species at 24 h or 48 h of exposure. After 24 h of exposure to doripenem at aTMICin the range of 12.5 to 37.5%,P. aeruginosaandA. baumanniipopulation profiles revealed mutants able to grow on 4× MIC-containing medium; such changes were further amplified by 48 h of exposure. Dose-fractionation experiments targetingTMICs of 12.5%, 25%, or 37.5% as six exposures, two exposures, or a single exposure over 48 h with a single strain ofP. aeruginosaindicated that changes in population profiles were greatest with multiple exposures atTMICtargets of 12.5 or 25%. In contrast, multiple exposures at 37.5%TMICmost effectively suppressed total bacterial counts and changes in population profiles. Simulations of human doses of doripenem of 500 mg, 1,000 mg, 2,000 mg, and 3,000 mg every 8 h over 96 h showed marked initial killing up to 6 h but growback thereafter. Changes in population profiles occurred only in the regimen of 500 mg every 8 h againstP. aeruginosabut occurred with all dose regimens forA. baumanniistrains. A doripenemTMICof ≥40 to 50% is maximally effective in killingP. aeruginosaorA. baumanniiand suppressing changes in population profiles in short-term experiments for up to 48 h; however, aTMICof 12.5 to 25% amplifies population changes, especially with exposures every 8 h. In longer-term experiments, up to 96 h, even doripenem doses of 4 to 6 times those used in human studies proved incapable of pathogen eradication and prevention of changes in population profiles. The association of aTMICof 25 to 37.5% with changes in population profiles has implications in terms of future clinical breakpoint setting.

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