scholarly journals COMPARISON OF IN VITRO ACTIVITY OF COLISTIN WITH CEFTOLOZANE/TAZOBACTAM AGAINST MULTI DRUG RESISTANT PSEUDOMONAS AERUGINOSA “A LAST LINE TREATMENT AGAINST MDR”

Author(s):  
K. M. Anwarul Islam ◽  
Muhammad Aitmaud Uddolah Khan ◽  
Sara Azhar ◽  
Muhammad Rashid Ahmed ◽  
Sumreen Khurram ◽  
...  

Objectives To evaluate and compare in vitro activity of Ceftolazane / Tazobactum and Colistin against Multi Drug Resistant (MDR) strains of Pseudomonas aeruginosa. Methodology After ethical approval this in vitro cross-sectional study was conducted from October 2017 to April 2018. Routine samples of pus, wound swabs, blood, tracheal aspirates and urine were collected and received from the in-patient and out-patient clinics. All the samples were submitted for culture and sensitivity testing at the microbiology laboratory of Ziauddin University Hospital, North Nazimabad campus. All the samples were processed according to the provided microbiological procedures, CLSI Guidelines 2018.  Results Forty sample from the out-patient clinics represented pre-dominance of Multi Drug Resistant strains of Pseudomonas aeruginosa (which was found to be 41.2%). On culture and sensitivity testing, it was observed that 60% of the MDR strains of P. aeruginosa were susceptible to Ceftolazane / Tazobactum which was markedly comparable to the susceptibility shown by Colistin (99%).Statistically, P value was highly significant and was found to be 0.0001. Conclusion Colistin showed superior activity as compared to Ceftolazane / Tazobactum against MDR isolates of P. aeruginosa. Thus, Colistin has proven to be a possible and important alternative against MDR isolates of P. aeruginosa, but due to its narrow therapeutic window and toxicity profile this drug can be used only when there is no working alternative, or the infection is severely debilitating.  

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S581-S582
Author(s):  
Patrick James Nolan ◽  
Tiffeny Smith ◽  
James D Finklea ◽  
Leah Cohen ◽  
Raksha Jain

Abstract Background Pseudomonas aeruginosa is a commonly isolated pathogen in adults with cystic fibrosis (CF). Antimicrobial resistance is an escalating problem due to chronic colonization and frequent antimicrobial exposure. Ceftolozane–tazobactam (C/T) and ceftazidime–avibactam (CZA) exhibit promising activity against antimicrobial-resistant organisms, including P. aeruginosa. In this study, we compared in vitro activity of C/T and CZA against P. aeruginosa isolated from respiratory cultures obtained from adult patients with CF. Methods This is a retrospective study of respiratory cultures positive for P. aeruginosa collected from adult CF patients between January 1, 2015 to November 30, 2018. The first isolate per patient per year that underwent susceptibility testing for C/T, CZA, and colistin were included in the study. All isolates underwent in-house susceptibility testing for 9 anti-pseudomonal agents according to the methodology established by the Clinical Laboratory Standards Institute (CLSI). Susceptibility testing of C/T, CZA, and colistin were performed by a reference lab. Isolates were classified into 3 drug-resistant categories using the following definition: multidrug-resistant (MDR) non-susceptible (NS) to ≥1 agent in ≥3 different antimicrobial classes, extensive drug-resistant (XDR) NS to 4 or 5 different classes, and pan drug-resistant (PDR) NS to all 6 classes except colistin. Results Forty-two P. aeruginosa respiratory isolates from 32 patients with CF were included. The overall susceptibility to C/T and CZA was 59.5% and 42.9%, respectively. Thirty-eight (90%) isolates were considered MDR with susceptibility of 55.3% to C/T and 44.7% to CZA. Among the 11 XDR isolates, susceptibility to C/T was 81.8% vs. CZA 72.7%. Susceptibility to C/T vs. CZA was also higher (37.5% vs. 25%) among the 24 PDR isolates. Conclusion Among P. aeruginosa isolated from CF respiratory cultures, C/T appears to have better in vitro activity compared with CZA, and remained true among isolates considered XDR and PDR. These results suggest using C/T while awaiting susceptibilities when standard anti-pseudomonal agents cannot be used. Future studies evaluating clinical outcomes for the treatment of pulmonary CF exacerbations are needed to assess the applicability of in vitro susceptibility data. Disclosures All authors: No reported disclosures.


Author(s):  
Carolina S. Nodari ◽  
Fernanda F. Santos ◽  
Mariana N.L. Kurihara ◽  
Tiago B. Valiatti ◽  
Rodrigo Cayô ◽  
...  

Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.


2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dae Hun Kim ◽  
Su-Young Kim ◽  
Hee Jae Huh ◽  
Nam Yong Lee ◽  
Won-Jung Koh ◽  
...  

ABSTRACT We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii. Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.


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