Abstract:
:Purpose: The rapid emergence of multidrug-resistant (MDR) bacteria and the lack of new therapies to eliminate them poses a major threat to global health. With the alarming rise in antimicrobial resistance (AMR), focus has now shifted to the use of the polymyxin class of antibiotics as the last line of defense for treatment of Gram-negative infections. Unfortunately, the growing resistance of bacteria against polymyxins is threatening the treatment of MDR infections, necessitating the need for novel strategies. The objective of this study was to determine if combination of polymyxin (polymyxin B or colistin) with a nonantibiotic small molecule AR-12, a celecoxib derivative that is devoid of cyclooxygenase 2 (COX-2) inhibitory activities, can be an effective strategy against polymyxin-resistant MDR bacteria. Methods: Growth inhibition studies, time-kill assays and permeability assays were conducted to investigate the effect of AR-12 on the antibacterial activity of polymyxins. Results: Growth studies were performed on a panel of polymyxin-resistant MDR strains using the combination of AR-12 with either colistin or polymyxin B. The combination treatment had no effect on strains that have inherent polymyxin resistance; however, AR-12 was effective in lowering the minimal inhibitory concentration (MIC) of polymyxins by 4-60-fold in several strains that had acquired polymyxin resistance. Time-kill assays using the combination of AR-12 and colistin with select MDR strains suggest rapid killing and bactericidal activity, while the permeability assays using fluorescently labeled dansylated polymyxin and 1-N-phenylnaphthylamine (NPN) in these MDR strains suggest that AR-12 can potentiate the antibacterial activity of polymyxins by possibly altering the bacterial outer membrane via modification of lipopolysaccharide and thereby improving the uptake of polymyxins. Conclusion: Our studies indicate that the combination of AR-12 and polymyxin is effective in targeting select Gram-negative bacteria that have acquired polymyxin resistance. Further understanding of the mechanism of action of AR-12 will provide new avenues for developing narrow-spectrum antibacterials to target select Gram-negative MDR bacteria. Importantly, our studies show that the use of nonantibiotic small molecules in combination with polymyxins is an attractive strategy to counter the growing resistance of bacteria to polymyxins.
journal_name
Infect Drug Resistjournal_title
Infection and drug resistanceauthors
Krishnamurthy M,Lemmon MM,Falcinelli EM,Sandy RA,Dootz JN,Mott TM,Rajamani S,Schaecher KE,Duplantier AJ,Panchal RGdoi
10.2147/IDR.S196874subject
Has Abstractpub_date
2019-05-27 00:00:00pages
1393-1405issn
1178-6973pii
196874journal_volume
12pub_type
杂志文章abstract:Purpose:This study examined patient- and hospital-level predictor variables that contribute to worse clinical and economic outcomes in patients with carbapenem-nonsusceptible respiratory infections. Patients and Methods:Electronic data (January 2013 to September 2015) were from 78 US hospitals. Nonduplicate, gram-nega...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S236026
更新日期:2020-03-09 00:00:00
abstract:Purpose:To assess the efficacy of amoxicillin, tetracycline, high-dose metronidazole, and a proton-pump inhibitor for third-line Helicobacter pylori eradication. Methods:We enrolled 70 consecutive patients who had registered, failed to respond to two rounds of H. pylori eradication, and undergone endoscopy for H. pylo...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S185511
更新日期:2018-10-30 00:00:00
abstract::COVID-19 is an emerging disease all over the world and spreading at an unpredicted rate, resulting in significant influences on global economies and public health. Clinical, laboratory, and imaging characteristics have been partially described in some observational studies. Not enough systematic reviews on predictors ...
journal_title:Infection and drug resistance
pub_type: 杂志文章,评审
doi:10.2147/IDR.S261159
更新日期:2020-06-26 00:00:00
abstract::Tuberculosis remains the world's second leading infectious cause of death, with nearly one-third of the global population latently infected. Treatment of latent tuberculosis infection is a mainstay of tuberculosis-control efforts in low-to medium-incidence countries. Isoniazid monotherapy has been the standard of care...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S29180
更新日期:2012-01-01 00:00:00
abstract:Background:Evidence suggests that genetic variations of exon 1 of mannose-binding lectin 2 (MBL2) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between MBL2 exon 1 polymorphisms (rs1800450, rs1800451, and rs5030737) and TB risk, but yielded inconclusive results. Method:We con...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S168465
更新日期:2018-08-20 00:00:00
abstract:INTRODUCTION:The characteristics and antimicrobial resistance profiles of Staphylococcus aureus differs according to geographical regions and in relation to antibiotic usage. The aim of this study was to determine the biochemical characteristics of the prevalent S. aureus from Ekiti State, Nigeria, and to evaluate thre...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S48809
更新日期:2013-08-20 00:00:00
abstract:Background:Hepatitis E virus (HEV) is an emerging infectious agent that causes acute hepatitis in developing and developed countries. Diagnosis of HEV infection has not been routinely done in Egyptian hospitals, and clinicians do not prescribe ribavirin (RBV) for acute hepatitis cases of unknown etiology (AHUE). We aim...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S289766
更新日期:2021-01-12 00:00:00
abstract:Purpose:This study aims to 1) describe the distribution characteristics of teicoplanin trough concentration (Cmin) and explore the related influencing factors and 2) evaluate the nephrotoxicity of teicoplanin in children. Patients and Methods:A cohort of children who were treated with teicoplanin intravenously were in...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S272982
更新日期:2020-11-12 00:00:00
abstract:Background:Flomoxef is potentially effective against β-lactamase-producing Enterobacteriaceae because limited clinical data demonstrate its effectiveness against Enterobacteriaceae bloodstream infections (BSIs) based on its minimum inhibitory concentrations (MICs). This study was conducted to determine the optimal brea...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S185670
更新日期:2018-11-27 00:00:00
abstract::Inorganic polyphosphate (polyP) and its metabolic enzymes are important in several cellular processes related with virulence and antibiotic susceptibility. Accordingly, bacterial polyP synthesis has been proposed as a good target for designing novel antivirulence molecules as alternative to conventional antibiotics. I...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S181906
更新日期:2019-07-22 00:00:00
abstract:Objective:To genetically characterize clusters of virulence factors (VFs) among extended spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and assess whether these clusters are associated with genetic determinants or clinical outcomes. Methods:One hundred forty-eight E. coli and 82 K. pn...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S179134
更新日期:2018-12-31 00:00:00
abstract:Background and objective:Acinetobacter baumannii (A. baumannii) is a common nosocomial pathogen, which developed multi-drug-resistance to different classes of antibiotics including carbapenems. This study examined ten common carbapenemase genes among 32 carbapenem-resistant A. baumannii clinical isolates recovered from...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S206691
更新日期:2019-10-03 00:00:00
abstract:Background:Broad-scale evidence has shown the significant association between ambient air pollutants and the development of tuberculosis (TB). However, the impact of air quality on the risk of TB in Taiwan is still poorly understood. Objective:To develop a probabilistic integrated population-level risk assessment appr...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S227823
更新日期:2019-12-06 00:00:00
abstract:Introduction:Candida species, one among the opportunistic fungi, has become a common pathogen causing vaginal thrush and nosocomial bloodstream infections (BSIs). This study aims to evaluate the prevalence and antifungal susceptibility of various Candida species and slime production by Candida species in BSIs and vulvo...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S179462
更新日期:2018-11-23 00:00:00
abstract:Background:The timely and accurate diagnosis of infected nonunion is challenging, and there is a need for more efficient biomarkers. Previous studies have shown that fibrinogen plays an important role in mediating inflammation in bacterial infections and, therefore, could be a valuable biomarker for infected nonunion. ...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S269719
更新日期:2020-11-04 00:00:00
abstract:Objective:To explore the composition of the ocular microbiome in normal subjects and patients with Meibomian gland dysfunction (MGD). Subjects and methods:Seventy subjects (140 eyes) were enrolled in our study. Signs of dry eye were evaluated and bacterial species in the conjunctival sac (CS) and Meibomian gland (MG) ...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S162135
更新日期:2018-10-11 00:00:00
abstract:Purpose:Infections, in particular with multidrug-resistant organisms, are a burden for inpatient and outpatient care and the whole community. The pathogens "roam" with patients and their relatives, forming an epidemiological bridge between different care facilities. Patients could play an important role in infection co...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S178922
更新日期:2018-12-04 00:00:00
abstract:Background:Leishmaniasis is an infectious disease common in tropical and subtropical regions caused by the genus Leishmania, which is transmitted by the bite of female sandflies. In this study, we evaluate the anti-leishmanial effect of recombinant Clostridium α-toxin protein alone and the combination with glucantime t...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S257561
更新日期:2020-07-15 00:00:00
abstract::While MIC distributions and percent susceptibility for cefepime and ceftazidime are generally similar among Pseudomonas aeruginosa, we noted an increasing discordance in susceptibility favoring ceftazidime at our hospital. Quantitative reverse transcriptase-polymerase chain reaction was utilized to explore overexpress...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/idr.s4418
更新日期:2008-01-01 00:00:00
abstract:Background:The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide devastating effect with a diagnostic challenge. Identifying risk factors of severity aids in assessment for the need of early hospitalization. We aimed to demonstrate, for the first time, the clinical, laborator...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S272605
更新日期:2020-10-05 00:00:00
abstract:Background:Tuberculosis is a communicable disease that is a major cause of ill health, one of the top 10 causes of death worldwide, and the leading cause of death from a single infectious agent, even ranking above human immuno-deficiency virus (HIV/AIDS). Objective:To assess the prevalence and associated risk factor...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S248059
更新日期:2020-05-21 00:00:00
abstract:Objectives:We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017. Materials and methods:Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S175679
更新日期:2018-10-26 00:00:00
abstract:BACKGROUND:Lyme disease is a tick-borne illness caused by the spirochete Borrelia burgdorferi. Although antibiotic therapy is usually effective early in the disease, relapse may occur when administration of antibiotics is discontinued. Studies have suggested that resistance and recurrence of Lyme disease might be due t...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S19201
更新日期:2011-01-01 00:00:00
abstract:Background:Ethiopia is one of the 22 high tuberculosis burden countries. In our country. there are limited published data to show the trend analysis of tuberculosis. Hence, we designed this trend analysis to fill the information gap in our study area. Institutional based retrospective cross-sectional study was employed...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S239717
更新日期:2020-02-24 00:00:00
abstract:Background:Recurrent tuberculosis (TB) following TB treatment completion in HIV-infected individuals remains a major public health burden. We assessed the role of various risk factors in mediating the development of recurrent TB and subsequent resistance to antiretroviral therapy and anti-TB drugs. Patients and method...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S150644
更新日期:2018-09-05 00:00:00
abstract::Background: The widespread use of antibiotics has resulted in a high incidence of antibiotic-associated diarrhea (AAD); moreover, the AAD-associated mortality rates have also increased. The effect of combined antibiotic administration on AAD in critically ill patients was analyzed to assist in antibiotic selection for...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S194715
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Antimicrobial drug resistance is a global issue that affects health, economic, and social development. The problem has been attributed to misuse of antimicrobial agents. PURPOSE:To identify the agents of bacterial infection in Ghana, determine their antibiogram, and the possibility of setting up a surveilla...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S21769
更新日期:2011-01-01 00:00:00
abstract::Echinocandin antifungal agents have become the first-line therapy for invasive candidiasis (IC) in many countries. Despite their increasing use, resistance to this class of drug is, overall, still uncommon. Here, we report two patients from the People's Republic of China with IC, one with infection caused by pan-echin...
journal_title:Infection and drug resistance
pub_type: 杂志文章
doi:10.2147/IDR.S152785
更新日期:2018-01-23 00:00:00
abstract::Tetracyclines have come a long way since they became available almost seven decades ago, with numerous enhancements allowing new agents to overcome bacterial mechanisms of resistance. However, these enhancements come with toxicities and pharmacokinetic disadvantages such as the gastrointestinal side-effects and poor o...
journal_title:Infection and drug resistance
pub_type: 杂志文章,评审
doi:10.2147/IDR.S171352
更新日期:2019-07-02 00:00:00
abstract::Raoultella ornithinolytica is an encapsulated Gram-negative, oxidase-negative, catalase-positive, aerobic, non-motile rod that belongs to the Enterobacteriaceae family. This bacterium was initially classified in the genus Klebsiella as Klebsiella ornithinolytica, until the creation of the genus Raoultella in 2001. R. ...
journal_title:Infection and drug resistance
pub_type: 杂志文章,评审
doi:10.2147/IDR.S191387
更新日期:2020-04-15 00:00:00