In VitroAntibiotic Susceptibility Pattern of Non-diphtheriae CorynebacteriumIsolates in Ontario, Canada, from 2011 to 2016

ABSTRACTNon-diphtheriae Corynebacterium-associated disease has been increasingly observed and often presents a conundrum to the treating physician. Analysis of antibiotic susceptibility testing data for 1,970 clinicalCorynebacteriumisolates received between 2011 and 2016 revealed that empirical drug treatment options are limited to vancomycin and linezolid.Corynebacterium striatumwas the most frequently observed species during this study period, along withC. amycolatumandC. pseudodiphtheriticum/C. propinquum. Low levels of susceptibility to penicillin (14.5%), erythromycin (15.1%), and clindamycin (8.7%) were observed for non-diphtheriae Corynebacteriumspecies, while 3.0% of isolates were not susceptible to daptomycin. Similarly, 26.9% and 38.1% ofCorynebacteriumisolates were susceptible to ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. Our data show much lower susceptibility to penicillin than previously reported in the literature and an increasing number of isolates resistant to daptomycin, highlighting the need for continued antibiotic surveillance studies for appropriate patient management and treatment success.

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Real-World Experience with Echinocandin MICs against Candida Species in a Multicenter Study of Hospitals That Routinely Perform Susceptibility Testing of Bloodstream Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02163-13 ◽

2014 ◽

Vol 58 (4) ◽

pp. 1897-1906 ◽

Cited By ~ 51

Author(s):

Gregory A. Eschenauer ◽

M. Hong Nguyen ◽

Shmuel Shoham ◽

Jose A. Vazquez ◽

Arthur J. Morris ◽

...

Keyword(s):

Retrospective Study ◽

New Zealand ◽

Multicenter Study ◽

Susceptibility Testing ◽

Broth Microdilution ◽

Content Type ◽

Future Studies ◽

Interlaboratory Variability ◽

Testing Data ◽

Resistance Rates

ABSTRACTReference broth microdilution methods ofCandidaechinocandin susceptibility testing are limited by interlaboratory variability in caspofungin MICs. Recently revised Clinical and Laboratory Standards Institute (CLSI) breakpoint MICs for echinocandin nonsusceptibility may not be valid for commercial tests employed in hospital laboratories. Indeed, there are limited echinocandin susceptibility testing data from hospital laboratories. We conducted a multicenter retrospective study of 9 U.S., Australian, and New Zealand hospitals that routinely testedCandidabloodstream isolates for echinocandin susceptibility from 2005 to 2013. Eight hospitals used Sensititre YeastOne assays. TheCandidaspp. wereC. albicans(n= 1,067),C. glabrata(n= 911),C. parapsilosis(n= 476),C. tropicalis(n= 185),C. krusei(n= 104), and others (n= 154). Resistance and intermediate rates were ≤1.4% and ≤3%, respectively, for each echinocandin againstC. albicans,C. parapsilosis, andC. tropicalis. Resistance rates amongC. glabrataandC. kruseiisolates were ≤7.5% and ≤5.6%, respectively. Caspofungin intermediate rates amongC. glabrataandC. kruseiisolates were 17.8% and 46.5%, respectively, compared to ≤4.3% and ≤4.4% for other echinocandins. Using CLSI breakpoints, 18% and 19% ofC. glabrataisolates were anidulafungin susceptible/caspofungin nonsusceptible and micafungin susceptible/caspofungin nonsusceptible, respectively; similar discrepancies were observed for 38% and 39% ofC. kruseiisolates. If only YeastOne data were considered, interhospital modal MIC variability was low (within 2 doubling dilutions for each agent). In conclusion, YeastOne assays employed in hospitals may reduce the interlaboratory variability in caspofungin MICs againstCandidaspecies that are observed between reference laboratories using CLSI broth microdilution methods. The significance of classifying isolates as caspofungin intermediate and anidulafungin/micafungin susceptible will require clarification in future studies.

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Caspofungin MICs Correlate with Treatment Outcomes among Patients with Candida glabrata Invasive Candidiasis and Prior Echinocandin Exposure

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00136-13 ◽

2013 ◽

Vol 57 (8) ◽

pp. 3528-3535 ◽

Cited By ~ 70

Author(s):

Ryan K. Shields ◽

M. Hong Nguyen ◽

Ellen G. Press ◽

Cassaundra L. Updike ◽

Cornelius J. Clancy

Keyword(s):

Treatment Outcomes ◽

Sensitivity And Specificity ◽

Invasive Candidiasis ◽

Candida Glabrata ◽

Susceptibility Testing ◽

Treatment Success ◽

Resistant Isolate ◽

Content Type ◽

Sterile Site ◽

Independent Risk Factors

ABSTRACTMutations inCandida glabrata FKSgenes, which encode the echinocandin target enzyme, are independent risk factors for treatment failures during invasive candidiasis. We retrospectively compared the ability of caspofungin susceptibility testing methods to identifyC. glabrataFKSmutant isolates and predict outcomes among patients at our center. Eight percent (10/120) of sterile-siteC. glabrataisolates harboredFKS1(n= 3) orFKS2(n= 7) mutations, including 32% (10/32) recovered from patients with prior echinocandin exposure. Median echinocandin exposures for mutant and nonmutant isolates were 55 (range, 7 to 188) and 13 (3 to 84) days, respectively (P= 0.004). Sensitivity and specificity of the CLSI caspofungin resistance breakpoint MIC (>0.12 μg/ml by broth microdilution using RPMI medium [BMD-RPMI]) were 90% (9/10) and 3% (3/110), respectively, for identifyingFKSmutants. Sensitivity and specificity of receiver-operator characteristic (ROC) curve-derived breakpoints by BMD-RPMI, BMD-antibiotic medium 3, Etest, and YeastOne ranged from 70 to 100% and 89 to 95%, respectively; susceptibility rates varied from 83 to 90%. The 14-day echinocandin treatment success rate was 67% (44/66); failure was more likely with prior echinocandin exposure (P= 0.002) or infection with anFKSmutant (P= 0.0001) or echinocandin-resistant isolates by BMD-AM3, Etest, and YeastOne (P≤ 0.03). The failure rate among patients with prior exposure and infection with a resistant isolate was 91% (10/11); it was 22% (12/55) among others (P< 0.0001). In conclusion, ROC-derived caspofungin MIC breakpoints by several methods were sensitive and specific for identifyingC. glabrataFKSmutant isolates. Mutations were seen exclusively among patients with prior echinocandin exposure. A paradigm that considers prior echinocandin exposure and caspofungin MICs accurately classified treatment outcomes forC. glabratainvasive candidiasis.

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Diagnostic Accuracy of BD Phoenix CPO Detect for Carbapenemase Production in 190 Enterobacteriaceae Isolates

Journal of Clinical Microbiology ◽

10.1128/jcm.01043-18 ◽

2018 ◽

Vol 56 (12) ◽

Cited By ~ 11

Author(s):

Chiou Horng Ong ◽

Lasantha Ratnayake ◽

Michelle L. T. Ang ◽

Raymond Tzer Pin Lin ◽

Douglas Su Gin Chan

Keyword(s):

Confidence Interval ◽

Infection Control ◽

Diagnostic Accuracy ◽

Positive Result ◽

Sensitivity And Specificity ◽

Patient Management ◽

Susceptibility Testing ◽

Control Measures ◽

Content Type ◽

Infection Control Measures

ABSTRACT The rapid and accurate detection of carbapenemase-producing Enterobacteriaceae (CPE) is necessary for patient management and infection control measures. We compared the performance of the BD Phoenix CPO Detect with that of a homemade Carba NP assay and a modified carbapenem inactivation method (mCIM) by challenging all 3 assays with 190 isolates of Enterobacteriaceae with meropenem MICs of >0.125 mg/liter. A total of 160 isolates produced KPC-, IMI-1-, NDM-, IMP-, and OXA-type carbapenemases, while 30 isolates were negative for carbapenemase production. The sensitivity and specificity were 90.6% (95% confidence interval [CI], 85.0% to 94.7%) and 100.0% (95% CI, 88.4% to 100.0%), respectively, for the Carba NP; 100.0% (95% CI, 97.7% to 100.0%) and 96.7% (95% CI, 82.7% to 99.9%), respectively, for the mCIM; and 89.4% (95% CI, 83.5% to 93.7%) and 66.7% (95% CI, 47.2% to 82.7%), respectively, for the BD Phoenix CPO Detect. In particular, the BD CPO Detect failed to detect a significant number of CPE with IMI-1. While the BD Phoenix CPO Detect is able to classify carbapenemases and is built into routine susceptibility testing with the potential to reduce the time to CPE detection, its low specificity means that a positive result will need confirmatory testing by another method.

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A Multiplex Fluidic Chip for Rapid Phenotypic Antibiotic Susceptibility Testing

mBio ◽

10.1128/mbio.03109-19 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Pikkei Wistrand-Yuen ◽

Christer Malmberg ◽

Nikos Fatsis-Kavalopoulos ◽

Moritz Lübke ◽

Thomas Tängdén ◽

...

Keyword(s):

Broad Spectrum ◽

Antibiotic Susceptibility ◽

Bacterial Infections ◽

Susceptibility Testing ◽

Empirical Therapy ◽

Automated Image Analysis ◽

Antibiotic Susceptibility Testing ◽

Content Type ◽

Broad Spectrum Antibiotics ◽

Severe Infections

ABSTRACT Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality. To this end, we have developed a multiplex fluidic chip for rapid phenotypic antibiotic susceptibility testing of bacteria. A total of 21 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were acquired from the EUCAST Development Laboratory and tested against amikacin, ceftazidime, and meropenem (Gram-negative bacteria) or gentamicin, ofloxacin, and tetracycline (Gram-positive bacteria). The bacterial samples were mixed with agarose and loaded in an array of growth chambers in the chip where bacterial microcolony growth was monitored over time using automated image analysis. MIC values were automatically obtained by tracking the growth rates of individual microcolonies in different regions of antibiotic gradients. Stable MIC values were obtained within 2 to 4 h, and the results showed categorical agreement with reference MIC values as determined by broth microdilution in 86% of the cases. IMPORTANCE Prompt and effective antimicrobial therapy is crucial for the management of patients with severe bacterial infections but is becoming increasingly difficult to provide due to emerging antibiotic resistance. The traditional methods for antibiotic susceptibility testing (AST) used in most clinical laboratories are reliable but slow with turnaround times of 2 to 3 days, which necessitates the use of empirical therapy with broad-spectrum antibiotics. There is a great need for fast and reliable AST methods that enable starting targeted treatment within a few hours to improve patient outcome and reduce the overuse of broad-spectrum antibiotics. The multiplex fluidic chip for phenotypic AST described in the present study may enable data on antimicrobial resistance within 2 to 4 h, allowing for an early initiation of appropriate antibiotic therapy.

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Molecular Epidemiology of Colonizing and Infecting Isolates of Klebsiella pneumoniae

mSphere ◽

10.1128/msphere.00261-16 ◽

2016 ◽

Vol 1 (5) ◽

Cited By ~ 64

Author(s):

Rebekah M. Martin ◽

Jie Cao ◽

Sylvain Brisse ◽

Virginie Passet ◽

Weisheng Wu ◽

...

Keyword(s):

Bacterial Infections ◽

Intestinal Tract ◽

Susceptibility Testing ◽

Empirical Therapy ◽

Time Frame ◽

Hospitalized Patients ◽

Antibiotic Susceptibility Testing ◽

Subsequent Infection ◽

Content Type ◽

Life Threatening

ABSTRACT K. pneumoniae commonly infects hospitalized patients, and these infections are increasingly resistant to carbapenems, the antibiotics of last resort for life-threatening bacterial infections. To prevent and treat these infections, we must better understand how K. pneumoniae causes disease and discover new ways to predict and detect infections. This study demonstrates that colonization with K. pneumoniae in the intestinal tract is strongly linked to subsequent infection. This finding helps to identify a potential time frame and possible approach for intervention: the colonizing strain from a patient could be isolated as part of a risk assessment, and antibiotic susceptibility testing could guide empirical therapy if the patient becomes acutely ill. Klebsiella pneumoniae is among the most common causes of hospital-acquired infections and has emerged as an urgent threat to public health due to carbapenem antimicrobial resistance. K. pneumoniae commonly colonizes hospitalized patients and causes extraintestinal infections such as urinary tract infection, bloodstream infection (septicemia), and pneumonia. If colonization is an intermediate step before infection, then detection and characterization of colonizing isolates could enable strategies to prevent or empirically treat K. pneumoniae infections in hospitalized patients. However, the strength of the association between colonization and infection is unclear. To test the hypothesis that hospitalized patients become infected with their colonizing strain, 1,765 patients were screened for rectal colonization with K. pneumoniae, and extraintestinal isolates from these same patients were collected over a 3-month period in a cohort study design. The overall colonization prevalence was 23.0%. After adjustment for other patient factors, colonization was significantly associated with subsequent infection: 21 of 406 (5.2%) colonized patients later had extraintestinal infection, compared to 18 of 1,359 (1.3%) noncolonized patients (adjusted odds ratio [OR], 4.01; 95% confidence interval, 2.08 to 7.73; P < 0.001). Despite a high diversity of colonizing isolates, 7/7 respiratory, 4/4 urinary, and 2/5 bloodstream isolates from colonized patients matched the patient corresponding rectal swab isolates, based on wzi capsular typing, multilocus sequence typing (MLST), and whole-genome sequence analysis. These results suggest that K. pneumoniae colonization is directly associated with progression to extraintestinal infection. IMPORTANCE K. pneumoniae commonly infects hospitalized patients, and these infections are increasingly resistant to carbapenems, the antibiotics of last resort for life-threatening bacterial infections. To prevent and treat these infections, we must better understand how K. pneumoniae causes disease and discover new ways to predict and detect infections. This study demonstrates that colonization with K. pneumoniae in the intestinal tract is strongly linked to subsequent infection. This finding helps to identify a potential time frame and possible approach for intervention: the colonizing strain from a patient could be isolated as part of a risk assessment, and antibiotic susceptibility testing could guide empirical therapy if the patient becomes acutely ill.

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Susceptibility testing of non-tuberculous mycobacteria

Microbiology Australia ◽

10.1071/ma04430 ◽

2004 ◽

Vol 25 (4) ◽

pp. 30

Author(s):

Leo McKnight

Keyword(s):

Treatment Outcome ◽

Susceptibility Testing ◽

Treatment Success ◽

Clinical Situation ◽

Response To Treatment ◽

In Vitro Testing ◽

Testing Data ◽

The Common ◽

Predict Treatment Failure

There is little consensus about treatment for the diseases caused by the common non-tuberculous mycobacteria (NTM). Guidelines are based largely on retrospective, non-controlled studies. Where susceptibility testing data is available, in vitro testing often correlates poorly or not at all with the clinical response to treatment. Performing non validated susceptibility testing is likely to confuse treatment rather than aid it. In the clinical situation, the only valid indication for performance of susceptibility testing is if the test will produce a result that will help predict treatment outcome. A ?susceptible? result should predict treatment success with that drug. Conversely, the detection of resistance in a susceptibility test should predict treatment failure.

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Influenza A(H7N9) Virus Acquires Resistance-Related Neuraminidase I222T Substitution When Infected Mallards Are Exposed to Low Levels of Oseltamivir in Water

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00886-15 ◽

2015 ◽

Vol 59 (9) ◽

pp. 5196-5202 ◽

Cited By ~ 15

Author(s):

Anna Gillman ◽

Marie Nykvist ◽

Shaman Muradrasoli ◽

Hanna Söderström ◽

Michelle Wille ◽

...

Keyword(s):

Influenza A ◽

Treatment Options ◽

Sewage Treatment ◽

H7n9 Virus ◽

Oseltamivir Carboxylate ◽

Resistance Development ◽

Content Type ◽

Influenza Pandemics ◽

Low Levels

ABSTRACTInfluenza A virus (IAV) has its natural reservoir in wild waterfowl, and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely undegraded through sewage treatment to river water where waterfowl reside. In anin vivomallard (Anas platyrhynchos) model, we tested if low-pathogenic avian influenza A(H7N9) virus might become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected, and OC was added to their water, after which infection and transmission were maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype, and phenotype. Following mallard exposure to 2.5 μg/liter OC, the resistance-related neuraminidase (NA) I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increases in the 50% inhibitory concentration (IC50) for OC (P< 0.001) and zanamivir (P= 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions, leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. Prudent use of oseltamivir and resistance surveillance of IAVs in wild birds are warranted.

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Determination of MIC Quality Control Ranges for the Novel Gyrase Inhibitor Zoliflodacin

Journal of Clinical Microbiology ◽

10.1128/jcm.00567-19 ◽

2019 ◽

Vol 57 (9) ◽

Cited By ~ 1

Author(s):

Alita A. Miller ◽

Maria M. Traczewski ◽

Michael D. Huband ◽

Patricia A. Bradford ◽

John P. Mueller

Keyword(s):

Quality Control ◽

Susceptibility Testing ◽

The Novel ◽

Tier 2 ◽

Phase 3 ◽

Content Type ◽

Surveillance Studies ◽

Agar Dilution

ABSTRACT This report describes the results of two different, multilaboratory quality control (QC) studies that were used to establish QC ranges for the novel gyrase inhibitor zoliflodacin against the ATCC strains recommended by the Clinical and Laboratory Standards Institute (CLSI). Following the completion of an eight-laboratory, CLSI document M23-defined tier 2 study, the agar dilution MIC QC range for zoliflodacin against the Neisseria gonorrhoeae QC strain ATCC 49226 was defined as 0.06 to 0.5 μg/ml and was approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing. This QC range will be used for in vitro susceptibility testing of zoliflodacin during phase 3 human clinical trials and surveillance studies, and eventually it will be implemented in clinical labs. In a separate study, broth microdilution MIC quality control ranges for zoliflodacin against additional QC strains were determined to be 0.12 to 0.5 μg/ml for Staphylococcus aureus ATCC 29213, 0.25 to 2 μg/ml for Enterococcus faecalis ATCC 29212, 1 to 4 μg/ml for Escherichia coli ATCC 25922, 0.12 to 0.5 μg/ml for Streptococcus pneumoniae ATCC 49619, and 0.12 to 1 μg/ml for Haemophilus influenzae ATCC 49247. These MIC QC ranges were also approved by CLSI for use in future in vitro susceptibility testing studies against organisms other than N. gonorrhoeae.

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Determination of Disk Diffusion and MIC Quality Control Ranges for Nafithromycin (WCK 4873), a New Lactone-Ketolide

Journal of Clinical Microbiology ◽

10.1128/jcm.00972-17 ◽

2017 ◽

Vol 55 (10) ◽

pp. 3021-3027 ◽

Cited By ~ 4

Author(s):

Meredith A. Hackel ◽

James A. Karlowsky ◽

Dana Dressel ◽

Daniel F. Sahm

Keyword(s):

Quality Control ◽

Susceptibility Testing ◽

Disk Diffusion ◽

Tier 2 ◽

Phase 3 ◽

Content Type ◽

Surveillance Studies ◽

Testing Patient

ABSTRACTDisk diffusion and MIC quality control (QC) ranges were determined for nafithromycin, a new lactone-ketolide, following the completion of a nine-laboratory, Clinical and Laboratory Standards Institute (CLSI) document M23-defined tier 2 study. Five QC strains consistent with the spectrum of activity of nafithromycin were tested:Staphylococcus aureusATCC 25923 (disk only),S. aureusATCC 29213 (broth only),Enterococcus faecalisATCC 29212 (broth only),Streptococcus pneumoniaeATCC 49619 (disk and broth), andHaemophilus influenzaeATCC 49247 (disk and broth). Nafithromycin disk diffusion QC ranges were determined to be 25 to 31 mm forS. aureusATCC 25923, 25 to 31 mm forS. pneumoniaeATCC 49619, and 16 to 20 mm forH. influenzaeATCC 49247. Nafithromycin MIC QC ranges were determined to be 0.06 to 0.25 μg/ml forS. aureusATCC 29213, 0.016 to 0.12 μg/ml forE. faecalisATCC 29212, 0.008 to 0.03 μg/ml forS. pneumoniaeATCC 49619, and 2 to 8 μg/ml forH. influenzaeATCC 49247. All disk diffusion and MIC QC ranges established in this study were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing at their June 2015 meeting and were initially reported in the 2017 M100S document. The QC ranges established in this study should be used for determining thein vitroactivity of nafithromycin in phase 2 and phase 3 human clinical trials and subsequently for testing patient isolates and isolates in phase 4 surveillance studies.

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Hospital surveillance predicts community pneumococcal antibiotic resistance in Vietnam

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa276 ◽

2020 ◽

Vol 75 (10) ◽

pp. 2902-2906

Author(s):

V T T Dai ◽

J Beissbarth ◽

P V Thanh ◽

P T Hoan ◽

H N L Thuy ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antibiotic Susceptibility ◽

Susceptibility Testing ◽

Vaccine Trial ◽

Nationwide Survey ◽

Surveillance Data ◽

Antibiotic Prescribing ◽

Antibiotic Susceptibility Testing ◽

Population Demographics ◽

Testing Data

Abstract Background In Vietnam, Streptococcus pneumoniae is a leading cause of disease, including meningitis. Antibiotics are available without physician prescription at community pharmacies and rates of antibiotic non-susceptibility are high. Appropriate treatment and antibiotic stewardship need to be informed by surveillance data. Objectives To report community-based pneumococcal antibiotic susceptibility testing data from children enrolled in a pneumococcal conjugate vaccine trial in Ho Chi Minh City [the Vietnam Pneumococcal Project (ViPP)] and compare these with published hospital-based data from the nationwide Survey of Antibiotic Resistance (SOAR) to determine whether hospital surveillance data provide an informative estimate of circulating pneumococcal resistance. Methods Pneumococcal isolates from 234 nasopharyngeal swabs collected from ViPP participants at 12 months of age underwent antibiotic susceptibility testing using CLSI methods and the data were compared with SOAR data. Results Antibiotic susceptibility testing identified penicillin-non-susceptible pneumococci in 93.6% of pneumococcus-positive ViPP swabs (oral, non-meningitis breakpoints). Non-susceptibility to erythromycin, trimethoprim/sulfamethoxazole, clindamycin and tetracycline also exceeded 79%. MDR, defined as non-susceptibility to three or more classes of antibiotic, was common (94.4% of swabs). Low or no resistance was detected for ceftriaxone (non-meningitis breakpoints), ofloxacin and vancomycin. Antibiotic non-susceptibility rates in ViPP and SOAR were similar for several antibiotics tested. Conclusions A very high proportion of pneumococci carried in the community are MDR. Despite wide disparities in population demographics between ViPP and SOAR, the non-susceptibility rates for several antibiotics were comparable. Thus, with some qualification, hospital antibiotic susceptibility testing data in Vietnam can inform circulating pneumococcal antibiotic non-susceptibility in young children, the group at highest risk of pneumococcal disease, to guide antibiotic prescribing and support surveillance strategies.

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