Assessment of combination therapy by time kill curve analysis and chequerboard assay for treatment of multi-drug resistant Pseudomonas aeruginosa isolates

2013 ◽  
Vol 1 (2) ◽  
pp. 103-108 ◽  
Author(s):  
Meher Rizvi ◽  
Junaid Ahmed ◽  
Fatima Khan ◽  
Indu Shukla ◽  
Abida Malik
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Curve Analysis ◽  
Drug Resistant ◽  
Kill Curve ◽  
Time Kill

scholarly journals In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae

2019 ◽  
Vol 74 (12) ◽  
pp. 3521-3529 ◽  
Author(s):  
Sunniva Foerster ◽  
George Drusano ◽  
Daniel Golparian ◽  
Michael Neely ◽  
Laura J V Piddock ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Single Agent ◽  
Curve Analysis ◽  
Phase Iii ◽  
Transmitted Infection ◽  
Kill Curve ◽  
Time Kill ◽  
Selection Of ◽  
Selection Of Resistance

Abstract Objectives Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae. Methods The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time–kill curve analysis and selection-of-resistance studies. Results Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time–kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5–4 mg/L. Conclusions Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.

scholarly journals Utility of antimicrobial combination therapy with break-point checkerboard plate for treatment against multi-drug resistant Pseudomonas aeruginosa

2014 ◽  
Vol 63 (1) ◽  
pp. 53-58
Author(s):  
Tomoko MURASE ◽  
Hideharu HAGIYA ◽  
Yuto HARUKI ◽  
Naoto WATANABE ◽  
Miyako MAKI ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Break Point ◽  
Drug Resistant

scholarly journals Antimicrobial Effects of β-Lactams on Imipenem-Resistant Ceftazidime-Susceptible Pseudomonas aeruginosa

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Yu Mi Wi ◽  
Ji-Young Choi ◽  
Ji-Young Lee ◽  
Cheol-In Kang ◽  
Doo Ryeon Chung ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mrna Expression ◽  
Multilocus Sequence Typing ◽  
Resistance Mechanism ◽  
Content Type ◽  
Antimicrobial Effects ◽  
High Inoculum ◽  
The Republic ◽  
Kill Curve ◽  
Time Kill

ABSTRACT We studied the resistance mechanism and antimicrobial effects of β-lactams on imipenem-resistant Pseudomonas aeruginosa isolates that were susceptible to ceftazidime as detected by time-kill curve methods. Among 215 P. aeruginosa isolates from hospitalized patients in eight hospitals in the Republic of Korea, 18 isolates (23.4% of 77 imipenem-resistant isolates) were imipenem resistant and ceftazidime susceptible. Multilocus sequence typing revealed diverse genotypes, which indicated independent emergence. These 18 isolates were negative for carbapenemase genes. All 18 imipenem-resistant ceftazidime-susceptible isolates showed decreased mRNA expression of oprD, and overexpression of mexB was observed in 13 isolates. In contrast, overexpression of ampC, mexD, mexF, or mexY was rarely found. Time-kill curve methods were applied to three selected imipenem-resistant ceftazidime-susceptible isolates at a standard inoculum (5 × 105 CFU/ml) or at a high inoculum (5 × 107 CFU/ml) to evaluate the antimicrobial effects of β-lactams. Inoculum effects were detected for all three β-lactam antibiotics, ceftazidime, cefepime, and piperacillin-tazobactam, against all three isolates. The antibiotics had significant killing effects in the standard inoculum, but no effects in the high inoculum were observed. Our results suggest that β-lactam antibiotics should be used with caution in patients with imipenem-resistant ceftazidime-susceptible P. aeruginosa infection, especially in high-inoculum infections such as endocarditis and osteomyelitis.

scholarly journals Effect of Pulmonary Surfactant on Antimicrobial ActivityIn Vitro

2013 ◽  
Vol 57 (10) ◽  
pp. 5151-5154 ◽  
Author(s):  
R. Schwameis ◽  
Z. Erdogan-Yildirim ◽  
M. Manafi ◽  
M. A. Zeitlinger ◽  
S. Strommer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Respiratory Tract ◽  
Pulmonary Surfactant ◽  
Respiratory Tract Infections ◽  
Content Type ◽  
Kill Curve ◽  
Tract Infections ◽  
Time Kill

ABSTRACTTime-kill curve experiments were performed with linezolid, doripenem, tigecycline, moxifloxacin, and daptomycin againstStaphylococcus aureusand with colistin, moxifloxacin, and doripenem againstPseudomonas aeruginosato evaluate the effect of porcine pulmonary surfactant on antimicrobial activity. Pulmonary surfactant significantly impaired the activities of moxifloxacin and colistin. When antibiotics are being developed for respiratory tract infections, the method described here might be used to preliminarily quantify the effect of pulmonary surfactant on antimicrobial activity.

scholarly journals Time-Kill Evaluation of Antibiotic Combinations Containing Ceftazidime-Avibactam against Extensively Drug-Resistant Pseudomonas aeruginosa and Their Potential Role against Ceftazidime-Avibactam-Resistant Isolates

2021 ◽  
Author(s):  
María M. Montero ◽  
Sandra Domene Ochoa ◽  
Carla López-Causapé ◽  
Sonia Luque ◽  
Luisa Sorlí ◽  
...  
Keyword(s):  
Public Health ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Treatment ◽  
Health Problem ◽  
Potential Role ◽  
Public Health Problem ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Time Kill ◽  
Emergence Of Resistance

The emergence of resistance to antibiotics is a serious public health problem worldwide and can be a cause of mortality. For this reason, antibiotic treatment is compromised, and we have few therapeutic options to treat infections.

scholarly journals Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Yu Mi Wi ◽  
Kerryl E. Greenwood-Quaintance ◽  
Audrey N. Schuetz ◽  
Kwan Soo Ko ◽  
Kyong Ran Peck ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistance Rate ◽  
Content Type ◽  
Reverse Transcription Pcr ◽  
Carbapenem Resistant ◽  
Kill Curve ◽  
Time Kill

ABSTRACT Although carbapenems are effective for treating serious multidrug-resistant Pseudomonas aeruginosa infections, carbapenem-resistant P. aeruginosa (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemase-producing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168–172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004) were included. All had been previously shown to be negative for bla IMP, bla VIM, bla SPM, bla GIM, bla SIM, and bla KPC by PCR. In the prior study, expression of oprD, ampC, and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 non-carbapenemase-producing CRPA isolates, overall susceptibility to C/T was 95.2%, compared to 71.4%, 42.9%, 23.8%, 21.4%, and 2.4% for C/A, ceftazidime, piperacillin-tazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased oprD and increased mexB expression (5.1% versus 25.6%, P = 0.025, and 4.3% versus 34.8%, P = 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased oprD and increased ampC expression. C/T was active against 95.2% of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.

scholarly journals Antimicrobial activities of widely consumed herbal teas, alone or in combination with antibiotics: anin vitrostudy

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3467 ◽  
Author(s):  
Mayram Hacioglu ◽  
Sibel Dosler ◽  
Ayse Seher Birteksoz Tan ◽  
Gulten Otuk
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Bactericidal Effect ◽  
Antimicrobial Activities ◽  
Combination Studies ◽  
Kill Curve ◽  
Time Kill ◽  
Microbroth Dilution ◽  
Antagonistic Interactions

BackgroundBecause of increasing antibiotic resistance, herbal teas are the most popular natural alternatives for the treatment of infectious diseases, and are currently gaining more importance. We examined the antimicrobial activities of 31 herbal teas both alone and in combination with antibiotics or antifungals against some standard and clinical isolates ofPseudomonas aeruginosa,Acinetobacter baumannii,Escherichia coli,Klebsiella pneumoniae,Enterococcus faecalis, methicillin susceptible/resistantStaphylococcus aureusandCandida albicans.MethodsThe antimicrobial activities of the teas were determined by using the disk diffusion and microbroth dilution methods, and the combination studies were examined by using the microbroth checkerboard and the time killing curve methods.ResultsRosehip, rosehip bag, pomegranate blossom, thyme, wormwood, mint, echinacea bag, cinnamon, black, and green teas were active against most of the studied microorganisms. In the combination studies, we characterized all the expected effects (synergistic, additive, and antagonistic) between the teas and the antimicrobials. While synergy was observed more frequently between ampicillin, ampicillin-sulbactam, or nystatine, and the various tea combinations, most of the effects between the ciprofloxacin, erythromycin, cefuroxime, or amikacin and various tea combinations, particularly rosehip, rosehip bag, and pomegranate blossom teas, were antagonistic. The results of the time kill curve analyses showed that none of the herbal teas were bactericidal in their usage concentrations; however, in combination with antibiotics they showed some bactericidal effect.DiscussionSome herbal teas, particularly rosehip and pomegranate blossom should be avoided because of their antagonistic interactions with some antibiotics during the course of antibiotic treatment or they should be consumed alone for their antimicrobial activities.

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