Prevalence of metallo-β-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii isolated from burn wounds and in vitro activities of antibiotic combinations against these isolates

Burns ◽  
2005 ◽  
Vol 31 (6) ◽  
pp. 707-710 ◽  
Author(s):  
Ulku Altoparlak ◽  
Ferda Aktas ◽  
Demet Celebi ◽  
Zulal Ozkurt ◽  
Mufide N. Akcay
2015 ◽  
Vol 59 (4) ◽  
pp. 2280-2285 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones ◽  
David J. Farrell

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.


2020 ◽  
Vol 21 (2) ◽  
pp. 132-139
Author(s):  
A.A. Allam ◽  
A.M. El-shawadfy ◽  
W.A.E. Hassanein ◽  
E.H.A. Hamza ◽  
E.A. Morad ◽  
...  

Background: Infection of burn wounds by multidrug-resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of morbidity and mortality and remains one of the most challenging concerns for the burns unit. The aim of this study is purify and characterize the haemolysin produced by multidrug resistant P. aeruginosa PAO1 isolated from burn wounds. Methods: Isolation and identification of P. aeruginosa from burns was done by standard bacteriological methods. P. aeruginosa PAO1 was identified by PCR amplification and sequencing of the 16S rRNA gene. The haemolysin of P. aeruginosa PAO1 was purified by 70% ammonium sulphate precipitation followed by gel filtration on Sephadex G-100, and separation by SDS-Poly Acrylamide Gel Electrophoresis. In vivo toxicity of the purified haemolysin was determined by intraperitoneal injection of Swiss albino mice, and in vitro toxin-antitoxin neutralization test was performed as previously described. Results: The pure haemolysin had a molecular weight of 37 kDa, with maximum activity at 25°C for 30 minutes and stable within pH range of 4-9 (maximum activity at pH 7). The haemolysin was activated by Ca2+, Fe3+ and Cu2+. Intraperitoneal injection of mice with 0.5ml of haemolysin (128 HU/ml) caused 100% mortality while 0.5 and 0.1 ml of haemolytic titer (64 HU/ml) of the heated haemolysin (toxoid) caused 50% and 0% mortality respectively. In vitro toxin-antitoxin neutralization test revealed that anti-haemolysin antitoxin was present in the serum of the mice that were previously vaccinated with heated toxin. Conclusion: This study concluded that haemolysin can be a potential vaccine component for prevention of haemolysis caused by multidrug resistant P. aeruginosa in burn patients.Keywords: haemolysin, Pseudomonas aeruginosa, multidrug resistant organism


2012 ◽  
Vol 56 (10) ◽  
pp. 5009-5015 ◽  
Author(s):  
Karen E. Bowker ◽  
Alan R. Noel ◽  
Sharon G. Tomaselli ◽  
Heather Elliott ◽  
Alasdair P. MacGowan

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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