scholarly journals Impact of rapid susceptibility testing and antibiotic selection strategy on the emergence and spread of antibiotic resistance in gonorrhea

2017 ◽  
Author(s):  
Ashleigh R Tuite ◽  
Thomas L Gift ◽  
Harrell W Chesson ◽  
Katherine Hsu ◽  
Joshua A Salomon ◽  
...  

AbstractBackgroundIncreasing antibiotic resistance limits treatment options for gonorrhea. We examined the extent to which a hypothetical point-of-care (POC) test reporting antibiotic susceptibility profiles could slow the spread of resistance.MethodsWe developed a deterministic compartmental model describing gonorrhea transmission in a single-sex population with three antibiotics available to treat infections. Probabilities of resistance emergence on treatment and fitness costs associated with resistance were based on characteristics of ciprofloxacin, azithromycin, and ceftriaxone. We evaluated time to 1% and 5% prevalence of resistant strains among all isolates with: (1) empiric treatment (azithromycin plus ceftriaxone), and treatment guided by POC tests determining susceptibility to (2) ciprofloxacin only and (3) all three antibiotics.FindingsBased on current gonococcal susceptibility patterns in the United States, the model indicated that continued empiric dual antibiotic treatment without POC testing resulted in >5% of isolates being resistant to both azithromycin and ceftriaxone within 15 years. When either POC test was used in 10% of identified cases, this was delayed by 5 years. The three antibiotic POC test delayed the time to reach 1% prevalence of triply-resistant strains by 6 years, while the ciprofloxacin-only test resulted in no delay. Results were less sensitive to assumptions about fitness costs and test characteristics with increasing test uptake. The main limitation of this study is that we made simplifying assumptions to describe gonorrhea transmission and the emergence and spread of resistance in the population.ConclusionsRapid diagnostics that report antibiotic susceptibility have the potential to extend the usefulness of existing antibiotics for treatment of gonorrhea. Monitoring resistance patterns will be critical with the introduction of such tests.

2018 ◽  
Author(s):  
David McAdams ◽  
Kristofer Wollein Waldetoft ◽  
Christine Tedijanto ◽  
Marc Lipsitch ◽  
Sam P. Brown

AbstractRapid point-of-care resistance diagnostics (POC-RD) are a key tool in the fight against antibiotic resistance. By tailoring drug choice to infection genotype, doctors can improve treatment efficacy while limiting costs of inappropriate antibiotic prescription. Here we combine epidemiological theory and data to assess the potential of RD innovations in a public health context, as a means to limit or even reverse selection for antibiotic resistance. POC-RD can be used to impose a non-biological fitness cost on resistant strains, by enabling diagnostic-informed treatment and targeted interventions that reduce resistant strains’ opportunities for transmission. We assess this diagnostic-imposed fitness cost in the context of a spectrum of bacterial population biologies, and find that the expected impact varies from selection against resistance for obligate pathogens to marginal public health improvements for opportunistic pathogens with high ‘bystander’ antibiotic exposure during asymptomatic carriage (e.g. the pneumococcus). We close by generalizing the notion of RD-informed strategies to incorporate carriage surveillance information, and illustrate that coupling transmission-control interventions to the discovery of resistant strains in carriage can potentially select against resistance in a broad range of opportunistic pathogens.


1978 ◽  
Vol 24 (11) ◽  
pp. 1358-1365 ◽  
Author(s):  
P. D. Duck ◽  
J. R. Dillon ◽  
H. Lior ◽  
L. Eidus

The antibiotic susceptibility of 2609 Salmonella isolates, collected during the period 1975–1976, was tested and the relationships between antibiotic-resistance pattern, source of isolation, and serovar and phagovar were determined. Of 95 serovars examined, 40 were sensitive to all of the antibiotics tested. Salmonella typhimurium was the major contributor to multiple resistance from both human and non-human sources.Multiply resistant strains were not found from animal feed sources and, in addition, S. typhimurium, one of the most predominant serovars, was found in every source but animal feeds.In comparing phagovar with resistance patterns, certain correlations were found. Greater than 90% of phagovar 10 was sensitive to all antibiotics tested whereas over 80% of phagovars 3-aerogenic, 92, and 123 were multiply resistant.


2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Joseph D. Lutgring ◽  
Rocío Balbuena ◽  
Natashia Reese ◽  
Sarah E. Gilbert ◽  
Uzma Ansari ◽  
...  

ABSTRACT The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-β-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here, we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacterales collected from 30 U.S. states through the Centers for Disease Control and Prevention’s Antibiotic Resistance Laboratory Network. The aims of the study were to determine the susceptibility of these isolates to 32 currently available antibiotics using reference broth microdilution and to explore the in vitro activity of 3 combination agents that are not yet available. Categorical interpretations were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria. For agents without CLSI criteria, Food and Drug Administration (FDA) interpretive criteria were used. The percentage of susceptible isolates did not exceed 90% for any of the FDA-approved antibiotics tested. The antibiotics with breakpoints that had the highest in vitro activity were tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible); 18.2% of isolates were susceptible to aztreonam. All NDM-producing isolates tested were multidrug resistant, and 116 isolates were extensively drug resistant (42.2%); 207 (75.3%) isolates displayed difficult-to-treat resistance. The difficulty in treating infections caused by NDM-producing Enterobacterales highlights the need for containment and prevention efforts to keep these infections from becoming more common.


2013 ◽  
Vol 76 (1) ◽  
pp. 6-17 ◽  
Author(s):  
ROSS C. BEIER ◽  
TONI L. POOLE ◽  
DAYNA M. BRICHTA-HARHAY ◽  
ROBIN C. ANDERSON ◽  
KENNETH M. BISCHOFF ◽  
...  

The disinfectant and antibiotic susceptibility profiles of 344 Escherichia coli O157:H7 strains from cattle carcasses, feces, and hides and ground beef from the United States were determined. A low prevalence of antibiotic resistance was observed (14%). The highest prevalences of resistance were to sulfisoxazole (10.5%), tetracycline (9.9%), streptomycin (7%), and chloramphenicol (4.9%). Four strains were resistant to eight antibiotics (two strains from ground beef and one strain each from hide and preevisceration carcass swabs of cull cattle at harvest). Pulsed-field gel electrophoresis analysis of the E. coli O157:H7 strains revealed two major groups (designated 1 and 2) composed of 17 and 20 clusters, respectively. Clusters 1A, 1B, 1C, and 1G.1 were associated with multidrug-resistant strains. There was no observed correlation between disinfectant resistance and antibiotic resistance. Sixty-nine (20%) of the 344 strains were resistant to chlorhexidine or benzalkonium chloride or the MICs of benzyldimethyldodecylammonium chloride were elevated. Inducible resistance was observed at elevated concentrations of antibiotics (1.4%) and disinfectants (6.1%). The highest rate of disinfectant inducible resistance was to OdoBan, quaternary ammonium chlorides, and the surface disinfectants F25, FS512, and MG, which are used in dairies, restaurants, and food processing plants. High MICs (1,024 to 4,096 μg/ml) of acetic, lactic, and citric acids were found. The decreasing order of acid potency based on molar MICs (MICsmolar) was acetic, citric, and lactic acid. The correlation of the concentration of dissociated organic acids and MICsmolar strongly suggests that the observed inhibition of E. coli O157:H7 was primarily due to dissociated forms of the acids.


Author(s):  
Melahat Gürbüz ◽  
Emek Türkekul Şen ◽  
Cengiz Demir ◽  
Berrin Esen

Objective: Broad-spectrum antibiotics used in empirical treatment lead to an increase in multidrug-resistant bacteria in intensive care units and hospital wards. Cumulative antibiotic susceptibility reports can guide the correct selection of empirical therapy and development of antibiotic resistance policies. In this study, we aimed to prepare a one-year inpatient cumulative antibiotic susceptibility report for our hospital. Method: Identification of bacteria and antibiotic susceptibility tests were performed with the automated VITEK 2 (bioMérieux, France) system and antibiogram results were evaluated according to the recommendations of The European Committee on Antimicrobial Susceptibility Testing (EUCAST, 2021). The cumulative antibiotic susceptibility report has been prepared according to the criteria in the Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data (CLSI 2014, M39-A4). Results: In this study, 1490 isolates were analysed. Vancomycin, teicoplanin, linezolid, and tigecycline were effective against gram positive agents. While tigecycline and cefuroxime were effective against enteric Escherichia coli isolates, nitrofurantoin and meropenem can be used in empirical treatment in urinary enterics. It has been observed that the most effective antibiotics against Proteus mirabilis were meropenem and amikacin. It was found that among the enteric and urinary enteric bacteria, there was no antibiotic option to be preferred in empirical treatment against Klebsiella pneumoniae isolates. Tigecycline was the most effective antibiotic against Acinetobacter baumannii isolates, whereas tobramycin was the most effective antibiotic against Pseudomonas aeruginosa isolates. Conclusion: Empirical treatment options for gram-negative and gram-positive bacteria are limited, and we believe that close monitoring of cumulative antibiotic reports will improve and reduce antibiotic resistance rates.


mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
David W. Watson ◽  
Santiago L. Iglesias ◽  
Edward M. Vasarhelyi ◽  
David E. Heinrichs

ABSTRACT Osteoarthritis is the most prevalent joint disease in the United States, with many patients requiring surgical replacement of the affected joint. The number of joint arthroplasty procedures performed each year is increasing, and infection is a leading cause of implant failure. Staphylococcus aureus is the most frequently isolated organism associated with periprosthetic joint infections of the knee or hip, and due to the emergence of antibiotic-resistant strains, treatment options are limited. Here, we show that synovial fluid from osteoarthritic patients is iron restrictive toward S. aureus and, for strains representing the clonal lineages USA100, USA200, USA400, and USA600, bactericidal. Remarkably, community-associated methicillin-resistant S. aureus (CA-MRSA) strain USA300-LAC was highly resistant to synovial fluid killing but could be sensitized to killing by mutation of the GraXRS regulatory system and GraXRS-regulated mprF gene or by small-molecule inhibition of GraR. Thus, we propose the GraXRS-VraFG regulatory system and mprF as targets for future therapeutics for treatment of S. aureus bone and joint infections. IMPORTANCE Osteoarthritis, a degenerative disease that results in the breakdown of joint cartilage and underlying bone, is the most prevalent joint disease in the United States. Surgical intervention, including total joint replacement, is a clinically effective procedure that can help to restore the patient’s quality of life. Unfortunately, joint replacement procedures come with a risk of infection that is estimated to occur in 1 to 2% of cases, and periprosthetic joint infection (PJI) is a leading cause of implant failure, requiring revision surgery. Staphylococcus aureus is well known for its ability to cause PJIs and was found to be the most frequently isolated organism from PJIs of the knee or hip. Antibiotic-resistant strains can often limit treatment options. In this study, we demonstrate that the MRSA strain LAC can resist killing and grow in human synovial fluid from osteoarthritic knees. Furthermore, we show that the GraXRS regulatory system is required for the displayed synovial fluid resistance. We further demonstrate that a small-molecule inhibitor of GraR sensitizes LAC to synovial fluid, validating the Gra system as a therapeutic target for the treatment of PJIs in humans.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S315-S315
Author(s):  
Takafumi Sato ◽  
Masakatsu Tsuji ◽  
Krystyna M Kazmierczak ◽  
Meredith M Hackel ◽  
Roger Echols ◽  
...  

Abstract Background Antibiotic susceptibility surveillance is the foundation for selecting treatment options as well as immediate and long-term strategies for combating antimicrobial resistance. We have conducted three surveillance studies SIDERO-WT-2014/-2015/-2016 with approximately 30,000 Gram-negative strains isolated in North America and Europe between 2014 and 2017. Here, we present the latest data of molecular analysis on acquired carbapenemase genes and antibiotic susceptibility of 3691 meropenem-nonsusceptible strains in the surveillance studies. Methods Meropenem-nonsusceptible strains isolated in North America (n = 1009) and Europe (n = 2,682), consisting of 1,897 Acinetobacter baumannii, 1,154 Pseudomonas aeruginosa, 447 Klebsiella pneumoniae, and 193 other Enterobacteriaceae were tested. Conventional PCR was used to detect known carbapenemases. Cefiderocol MICs were determined by broth microdilution method using iron-depleted cation-adjusted Mueller–Hinton broth. Results The percentages of known carbapenemases detected in 3 main pathogens are shown in the Table. In A. baumannii complex, OXA-23 was predominant followed by OXA-24 in most countries. The detection rates of VIM in P. aeruginosa were ≥40% in Greece and Russia, but none of the strains in the United States carried VIM. In K. pneumoniae, the predominant carbapenemase varied among the countries, with KPC predominating in the USA, Greece and Italy, while OXA-48-like was dominant in Russia, Spain and Turkey. Cefiderocol MIC90 were ≤4 μg/mL against these 3 pathogens in all 6 countries, except for A. baumannii strains in Russia. Conclusion Carbapenemase detection rates, especially in P. aeruginosa and K. pneumoniae, were quite different among the countries. Cefiderocol demonstrated potent in vitro activity against meropenem-nonsusceptible strains irrespective of the presence of specific carbapenemases. Disclosures All authors: No reported disclosures.


2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Adriana R. Marques

ABSTRACT Lyme disease is a tick-borne illness caused by Borreliella (Borrelia) burgdorferi, and it is the most common vector-borne disease in the United States, with an estimated incidence of 300,000 cases per year. The currently recommended approach for laboratory support of the diagnosis of Lyme disease is a standard two-tiered (STT) algorithm comprised of an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA), followed by Western blotting (WB). The STT algorithm has low sensitivity in early infection, and there are drawbacks associated with the WB use in practice. Modified two-tiered (MTT) algorithms have been shown to improve the sensitivity of the testing in early disease while maintaining high specificity. In this issue of the Journal of Clinical Microbiology, A. Pegalajar-Jurado et al. (J Clin Microbiol 56:e01943-17, 2018, https://doi.org/10.1128/JCM.01943-17) report the results of their evaluation of the Liaison VlsE CLIA, the Captia B. burgdorferi IgG/IgM EIA, and the C6 B. burgdorferi (Lyme) EIA as MTT algorithms compared with results with the STT algorithm using the same tests as the first-tier test and the ViraStripe IgM and IgG WBs as the second-tier test. The results showed that all MTT algorithms had higher sensitivities than STT algorithms and were highly specific. These results showed that MTT approaches are a valid alternative to the currently recommended STT algorithm for serodiagnosis of Lyme disease, opening the door for the development of rapid diagnostics and point-of-care testing that can provide diagnostic information during the initial patient visit.


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