scholarly journals Bringing Antimicrobial Susceptibility Testing for New Drugs into the Clinical Laboratory: Removing Obstacles in Our Fight against Multidrug-Resistant Pathogens

2019 ◽  
Vol 57 (12) ◽  
Author(s):  
James E. Kirby ◽  
Thea Brennan-Krohn ◽  
Kenneth P. Smith
Keyword(s):  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Drug Approval ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Testing Methods ◽  
Clinical Laboratories ◽  
New Antibiotics ◽  
Multidrug Resistant Pathogens ◽  
Patient Use

ABSTRACT There are now several new antibiotics available to treat multidrug-resistant pathogens, and susceptibility testing methods for these drugs are increasingly available at the time of drug approval. However, lack of clarity regarding verification requirements remains a formidable barrier to introducing such testing in clinical laboratories, making these drugs practically unavailable for patient use. We propose a change in the framework for bringing in testing for new antibiotics, focusing on quality control rather than underpowered verification studies.

Antibacterial activity of bacteria isolated from Phragmites australis against multidrug-resistant human pathogens

2021 ◽  
Vol 16 (5) ◽  
pp. 291-303
Author(s):  
Vania Delfino ◽  
Carmela Calonico ◽  
Antonella Lo Nostro ◽  
Lara Mitia Castronovo ◽  
Sara Del Duca ◽  
...  
Keyword(s):  
Phragmites Australis ◽  
Multidrug Resistant ◽  
Antimicrobial Compounds ◽  
Bacterial Endophytes ◽  
Human Pathogens ◽  
Natural Sources ◽  
New Antibiotics ◽  
Multidrug Resistant Pathogens ◽  
New Compounds ◽  
Novel Antibiotics

Background: Rising number of multidrug-resistant human pathogens demands novel antibiotics: to this aim, unexplored natural sources are investigated to find new compounds. In this context, bacteria associated to medicinal plants, including Phragmites australis, might represent an important source of antimicrobial compounds. Materials & methods: In the present work, 21 bacterial endophytes isolated from P. australis roots were tested, by cross-streaking, for their inhibitory activity against 36 multidrug-resistant pathogens isolated from food, clinical patients and hospitals. Results & conclusion: Seven endophytes, belonging to Pseudomonas and Stenotrophomonas, were able to inhibit the growth of most of the target strains. In conclusion, this preliminary work could pave the way for the discovery of new antibiotics against superbugs.

scholarly journals Nonsusceptibility to Ceftazidime or Cefepime Can Predict Carbapenemase-Production Among Carbapenem-Resistant Pseudomonas aeruginosaa

2020 ◽  
Vol 41 (S1) ◽  
pp. s330-s331
Author(s):  
Snigdha Vallabhaneni ◽  
Jennifer Huang ◽  
Julian Grass ◽  
Sarah Malik ◽  
Amelia Bhatnagar ◽  
...  
Keyword(s):  
Drug Combination ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Carbapenem Resistance ◽  
The United States ◽  
Population Based ◽  
Molecular Testing ◽  
Carbapenem Resistant ◽  
Clinical Laboratories ◽  
Break Points

Background: In the United States, carbapenemases are rarely the cause of carbapenem resistance in Pseudomonas aeruginosa. Detection of carbapenemase production (CP) in carbapenem-resistant P. aeruginosa (CRPA) is critical for preventing its spread, but testing of many isolates is required to detect a single CP-CRPA. The CDC evaluates CRPA for CP through (1) the Antibiotic Resistance Laboratory Network (ARLN), in which CRPA are submitted from participating clinical laboratories to public health laboratories for carbapenemase testing and antimicrobial susceptibility testing (AST) and (2) laboratory and population-based surveillance for CRPA in 8 sites through the Emerging Infection Program (EIP). Objective: We used data from ARLN and EIP to identify AST phenotypes that can help detect CP-CRPA. Methods: We defined CRPA as P. aeruginosa resistant to meropenem, imipenem, or doripenem, and we defined CP-CRPA as CRPA with molecular identification of carbapenemase genes (blaKPC, blaIMP, blaNDM, or blaVIM). We applied CLSI break points to 2018 ARLN CRPA AST data to categorize isolates as resistant, intermediate, or susceptible, and we evaluated the sensitivity and specificity of AST phenotypes to detect CP among CRPA; isolates that were intermediate or resistant were called nonsusceptible. Using EIP data, we assessed the proportion of isolates tested for a given drug in clinical laboratories, and we applied definitions to evaluate performance and number needed to test to identify a CP-CRPA. Results: Only 203 of 6,444 of CRPA isolates (3%) tested through AR Lab Network were CP-CRPA harboring blaVIM (n = 123), blaKPC (n = 53), blaIMP (n = 16), or blaNDM (n = 13) genes. Definitions with the best performance were resistant to ≥1 carbapenem AND were (1) nonsusceptible to ceftazidime (sensitivity, 93%; specificity, 61%) (Table 1) or (2) nonsusceptible to cefepime (sensitivity, 83%; specificity, 53%). Most isolates not identified by definition 2 were sequence type 111 from a single-state blaVIM CP-CRPA outbreak. Among 4,209 CRPA isolates identified through EIP, 80% had clinical laboratory AST data for ceftazidime and 96% had clinical laboratory AST data for cefepime. Of 967 CRPA isolates that underwent molecular testing at the CDC, 7 were CP-CRPA; both definitions would have detected all 7. Based on EIP data, the number needed to test to identify 1 CP-CRPA would decrease from 135 to 42 for definition 1 and to 50 using definition 2. Conclusions: AST-based definitions using carbapenem resistance combined with ceftazidime or cefepime nonsusceptibility would rarely miss a CP-CRPA and would reduce the number needed to test to identify CP-CRPA by >60%. These definitions could be considered for use in laboratories to decrease the testing burden to detect CP-CRPA.Funding: NoneDisclosures: In the presentation we will discuss the drug combination aztreonam-avibactam and acknowledge that this drug combination is not currently FDA approved.

scholarly journals Antimicrobial resistance in coagulase-negative staphylococci isolated from subclinical mastitis in Ettawa Crossbred goat (PE) in Yogyakarta, Indonesia

2021 ◽  
Vol 22 (6) ◽  
Author(s):  
Widodo Suwito ◽  
WIDAGDO SRI NUGROHO ◽  
AGNESIA ENDANG TRI HASTUTI WAHYUNI ◽  
BAMBANG SUMIARTO
Keyword(s):  
Antimicrobial Resistance ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Subclinical Mastitis ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Diffusion Method ◽  
Disc Diffusion Method ◽  
Coagulase Negative Staphylococci ◽  
Resistance Patterns

Abstract. Suwito W, Nugroho WS, Wahyuni AETH, Sumiarto B. 2021. Antimicrobial resistance in coagulase-negative staphylococci isolated from subclinical mastitis in Ettawa Crossbred goat (PE) in Yogyakarta, Indonesia. Biodiversitas 22: 3418-3422. Subclinical mastitis (SCM) in Ettawa Crossbred Goat (PE) is most frequently caused by staphylococci with a significant reduction in milk yield. The aim of this study is to determine antimicrobial resistance patterns of coagulase-negative staphylococci (CoNS) from PE goat SCM. A total of 36 CoNS isolates originating from PE goat SCM were collected in semisolid tube use in this study. All CoNS isolates were further examined for antimicrobial susceptibility testing by the Kirby-Bauer disc diffusion method. Antibiotic susceptibility of CoNS isolated samples according to Clinical Laboratory Standards Institute (CLSI). The CoNS isolates showed the highest resistance rate against sulfamethoxazole (65%), ampicillin (55.56%), penicillin (45%), cefoxitin (33.33%), erythromycin (25%), oxytetracycline (20%), tetracycline (15%), gentamicin and neomycin (11.11%), while oxacillin was sensitive. The highest of multiple antimicrobials resistance observed 15% in ampicillin, penicillin and tetracycline, then 5-10% in ampicillin, penicillin, erythromycin, tetracycline and oxytetracycline. The majority of CoNS in this study were resistant to sulfamethoxazole and then, followed by ampicillin, penicillin, cefoxitin, erythromycin, oxytetracycline, tetracycline, gentamicin and neomycin. In addition, most isolates were penicillin-resistant and multidrug-resistant (MDR).

Multiresistente Bakterien: Antibiotikaverordnung und Reserveantibiotika

2018 ◽  
Vol 143 (09) ◽  
pp. 643-650 ◽  
Author(s):  
Winfried Kern
Keyword(s):  
Antibiotic Resistance ◽  
Food Production ◽  
One Health ◽  
Susceptibility Testing ◽  
Environmental Issues ◽  
Multidrug Resistant ◽  
Human Medicine ◽  
New Drugs ◽  
Adequate Treatment ◽  
Multidrug Resistant Organisms

AbstractAscertaining critical indications for antibiotics and rational prescribing can delay and minimize the spread of antibiotic resistance. Room for improvement lies in particular in a stricter indication, in shortening antibiotic treatment and in initiating more targeted therapies with narrow-spectrum drugs. Not all infections due to multidrug-resistant organisms require treatment with reserve drugs. Detailed susceptibility testing together with enhanced knowledge of pharmacokinetics and -dynamics are needed for adequate treatment decisions. There are some new drugs with interesting spectrum of activity in development. The problem of antimicrobial resistance in human medicine, however, must also be seen in the context of “One Health” interactions between various systems including environmental issues and food production.

scholarly journals Imcroporin, a New Cationic Antimicrobial Peptide from the Venom of the Scorpion Isometrus maculates

2009 ◽  
Vol 53 (8) ◽  
pp. 3472-3477 ◽  
Author(s):  
Zhenhuan Zhao ◽  
Yibao Ma ◽  
Chao Dai ◽  
Ruiming Zhao ◽  
SongRyong Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Lead Compound ◽  
Cationic Antimicrobial Peptide ◽  
Antibiotic Resistant ◽  
Multidrug Resistant Pathogens ◽  
Conventional Antibiotics

ABSTRACT The pace of resistance against antibiotics almost exceeds that of the development of new drugs. As many bacteria have become resistant to conventional antibiotics, new drugs or drug resources are badly needed to combat antibiotic-resistant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA). Antimicrobial peptides, rich sources existing in nature, are able to effectively kill multidrug-resistant pathogens. Here, imcroporin, a new antimicrobial peptide, was screened and isolated from the cDNA library of the venomous gland of Isometrus maculates. The MIC of imcroporin against MRSA was 50 μg/ml, 8-fold lower than that of cefotaxime and 40-fold lower than that of penicillin. Imcroporin killed bacteria rapidly in vitro, inhibited bacterial growth, and cured infected mice. These results revealed that imcroporin could be considered a potential anti-infective drug or lead compound, especially for treating antibiotic-resistant pathogens.

scholarly journals 1594. Ceftolozane–Tazobactam Demonstrates Higher In Vitro Susceptibility than Ceftazidime–Avibactam Against Pseudomonas aeruginosa Isolated from Respiratory Tract of Adult Cystic Fibrosis Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S581-S582
Author(s):  
Patrick James Nolan ◽  
Tiffeny Smith ◽  
James D Finklea ◽  
Leah Cohen ◽  
Raksha Jain
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Clinical Laboratory ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
In Vitro Susceptibility

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.

scholarly journals Evaluation of Calcium-Enhanced Media for Colistin Susceptibility Testing by Gradient Agar Diffusion and Broth Microdilution

2019 ◽  
Vol 58 (2) ◽  
Author(s):  
Daniel A. Green ◽  
Nenad Macesic ◽  
Anne-Catrin Uhlemann ◽  
Mabel Lopez ◽  
Stephania Stump ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Poor Performance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
High Rate ◽  
Broth Microdilution ◽  
Content Type ◽  
Agar Diffusion ◽  
Clinical Laboratories ◽  
Susceptible Patient

ABSTRACT Despite the increasing reliance on polymyxin antibiotics (polymyxin B and colistin) for treatment of multidrug-resistant Gram-negative infections, many clinical laboratories are unable to perform susceptibility testing due to the lack of accurate and reliable methods. Although gradient agar diffusion is commonly performed for other antimicrobials, its use for polymyxins is discouraged due to poor performance characteristics. Performing gradient agar diffusion with calcium enhancement of susceptibility testing media has been shown to improve the identification of polymyxin-resistant isolates with plasmid-mediated resistance (mcr-1). We therefore sought to evaluate the broad clinical applicability of this approach for colistin susceptibility testing by assessing a large and diverse collection of resistant and susceptible patient isolates collected from multiple U.S. medical centers. Among 217 isolates, the overall categorical and essential agreement for calcium-enhanced gradient agar diffusion were 73.7% and 65.5%, respectively, compared to the results for reference broth microdilution. Performance varied significantly by organism group, with agreement being highest for Enterobacterales and lowest for Pseudomonas aeruginosa. Nevertheless, even for Enterobacterales, there was a high rate of very major errors (9.2%). Performance was similarly poor for calcium-enhanced broth microdilution. While calcium enhancement did allow for more accurate categorization of mcr-1-resistant isolates, there were unacceptably high rates of errors for both susceptible and non-mcr-1-resistant isolates, raising serious doubts about the suitability of these calcium-enhanced methods for routine colistin susceptibility testing in clinical laboratories.

scholarly journals 710. In Vitro Activity and Performance of Available Susceptibility Testing Methods for Eravacycline Against Carbapenem-Resistant Enterobacteriaceae (CRE)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S319-S320
Author(s):  
Chelsea E Jones ◽  
Ellen G Kline ◽  
Minh-Hong Nguyen ◽  
Cornelius J Clancy ◽  
Ryan K Shields
Keyword(s):  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
In Vitro Activity ◽  
Testing Methods ◽  
And Performance ◽  
Susceptibility Breakpoint

Abstract Background Eravacycline (ERV) is a recently-approved, fully synthetic fluorocycline agent that demonstrates broad in vitro activity against multidrug-resistant pathogens. We sought to compare the activity of ERV with minocycline (MIN) and tigecycline (TGC) against diverse CRE clinical isolates, and to evaluate the performance of commercially-available susceptibility testing methods. Methods ERV, MIN, and TGC minimum inhibitory concentrations (MICs) were determined in triplicate by broth microdilution against previously characterized CRE isolates. ERV susceptibility was also measured by disk diffusion (20 µg disk; Mast Group) and MIC test strips (MTS; Liofilchem) according to manufacturer instructions. Results 148 CRE were tested, including 92 K. pneumoniae, 32 Enterobacter spp, 11 E. coli, 5 C. freundii, 4 K. oxytoca, and 4 S. marcescens. 72% of isolates harbored blaKPC, which encoded KPC-2 (n = 33), KPC-3 (n = 48), and other KPC variants (n = 22). 77% and 19% of isolates were resistant to meropenem and ceftazidime–avibactam, respectively. By BMD, the ERV, MIN, and TGC MIC range, MIC50 and MIC90 for shown in the Table. ERV MICs were ≥2-fold lower than MIN and TGC against 99% and 43% of isolates, respectively. ERV MICs did not vary by species or KPC-subtype. ERV MICs determined by BMD and MTS were well-correlated showing 89% essential agreement (MIC within one 2-fold dilution; Figure). The rate of categorical agreement (CA) was 73%. By comparison, the CA rate between BMD and disk diffusion was 78%. By both MTS and disk diffusion methods, susceptibility results clustered on either side of the susceptibility breakpoint. 50% of disk diffusion zones clustered between 14 and 16 millimeters (mm), which is 1 mm on either side of the susceptibility breakpoint (≥15 mm). Conclusion This study confirms the in vitro activity of ERV against CRE clinical isolates, which is comparable to TGC. ERV MTS demonstrated high rates of EA, but lower rates of CA. Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint. Disclosures All authors: No reported disclosures.

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