Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-30 (of 39 Records) |
Query Trace: Lonsway D [original query] |
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Antimicrobial Resistance Laboratory Network's multisite evaluation of the ThermoFisher Sensititre GN7F broth microdilution panel for antimicrobial susceptibility testing
Bhatnagar AS , Machado MJ , Patterson L , Anderson K , Abelman RL , Bateman A , Biggs A , Bumpus-White P , Craft B , Howard M , LaVoie SP , Lonsway D , Sabour S , Schneider A , Snippes-Vagnone P , Tran M , Torpey D , Valley A , Elkins CA , Karlsson M , Brown AC . J Clin Microbiol 2023 61 (12) e0079923 In 2017, the Centers for Disease Control and Prevention (CDC) established the Antimicrobial Resistance Laboratory Network to improve domestic detection of multidrug-resistant organisms. CDC and four laboratories evaluated a commercial broth microdilution panel. Antimicrobial susceptibility testing using the Sensititre GN7F (ThermoFisher Scientific, Lenexa, KS) was evaluated by testing 100 CDC and Food and Drug Administration AR Isolate Bank isolates [40 Enterobacterales (ENT), 30 Pseudomonas aeruginosa (PSA), and 30 Acinetobacter baumannii (ACB)]. We assessed multiple amounts of transfer volume (TV) between the inoculum and tubed 11-mL cation-adjusted Mueller-Hinton broth: 1 µL [tribe Proteeae (P-tribe) only] and 10, 30, and 50 µL, resulting in respective CFU per milliter of 1 × 10(4), 1 × 10(5), 3 × 10(5), and 5 × 10(5). Four TV combinations were analyzed: standard (STD) [1 µL (P-tribe) and 10 µL], enhanced standard (E-STD) [1 µL (P-tribe) and 30 µL], 30 µL, and 50 µL. Essential agreement (EA), categorical agreement, major error (ME), and very major error (VME) were analyzed by organism then TVs. For ENT, the average EA across laboratories was <90% for 7 of 15 β-lactams using STD and E-STD TVs. As TVs increased, EA increased (>90%), and VMEs decreased. For PSA, EA improved as TVs increased; however, MEs also increased. For ACB, increased TVs provided slight EA improvements; all TVs yielded multiple VMEs and MEs. For ENT and ACB, Minimum inhibitory concentrations (MICs) trended downward using a 1 or 10 µL TV; there were no obvious MIC trends by TV for PSA. The public health and clinical consequences of missing resistance warrant increased TV of 30 µL for the GN7F, particularly for P-tribe, despite being considered "off-label" use. |
Development of a broth microdilution method to characterize chlorhexidine mics among bacteria collected from 2005 to 2019 at three U.S. Sites
Lutgring JD , Grass JE , Lonsway D , Yoo BB , Epson E , Crumpler M , Galliher K , O'Donnell K , Zahn M , Evans E , Jacob JT , Page A , Satola SW , Smith G , Kainer M , Muleta D , Wilson CD , Hayden MK , Reddy S , Elkins CA , Rasheed JK , Karlsson M , Magill SS , Guh AY . Microbiol Spectr 2023 11 (3) e0413422 Chlorhexidine bathing to prevent transmission of multidrug-resistant organisms has been adopted by many U.S. hospitals, but increasing chlorhexidine use has raised concerns about possible emergence of resistance. We sought to establish a broth microdilution method for determining chlorhexidine MICs and then used the method to evaluate chlorhexidine MICs for bacteria that can cause health care-associated infections. We adapted a broth microdilution method for determining chlorhexidine MICs, poured panels, established quality control ranges, and tested Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex isolates collected at three U.S. sites. Chlorhexidine MICs were determined for 535 isolates including 129 S. aureus, 156 E. coli, 142 K. pneumoniae, and 108 E. cloacae complex isolates. The respective MIC distributions for each species ranged from 1 to 8 mg/L (MIC(50) = 2 mg/L and MIC(90) = 4 mg/L), 1 to 64 mg/L (MIC(50) = 2 mg/L and MIC(90) = 4 mg/L), 4 to 64 mg/L (MIC(50) = 16 mg/L and MIC(90) = 32 mg/L), and 1 to >64 mg/L (MIC(50) = 16 mg/L and MIC(90) = 64 mg/L). We successfully adapted a broth microdilution procedure that several laboratories were able to use to determine the chlorhexidine MICs of bacterial isolates. This method could be used to investigate whether chlorhexidine MICs are increasing. IMPORTANCE Chlorhexidine bathing to prevent transmission of multidrug-resistant organisms and reduce health care-associated infections has been adopted by many hospitals. There is concern about the possible unintended consequences of using this agent widely. One possible unintended consequence is decreased susceptibility to chlorhexidine, but there are not readily available methods to perform this evaluation. We developed a method for chlorhexidine MIC testing that can be used to evaluate for possible unintended consequences. |
Welder's Anthrax: A Tale of 2 Cases.
Hendricks K , Martines RB , Bielamowicz H , Boyer AE , Long S , Byers P , Stoddard RA , Taylor K , Kolton CB , Gallegos-Candela M , Roberts C , DeLeon-Carnes M , Salzer J , Dawson P , Brown D , Templeton-LeBouf L , Maves RC , Gulvik C , Lonsway D , Barr JR , Bower WA , Hoffmaster A . Clin Infect Dis 2022 75 S354-s363 Bacillus anthracis has traditionally been considered the etiologic agent of anthrax. However, anthrax-like illness has been documented in welders and other metal workers infected with Bacillus cereus group spp. harboring pXO1 virulence genes that produce anthrax toxins. We present 2 recent cases of severe pneumonia in welders with B. cereus group infections and discuss potential risk factors for infection and treatment options, including antitoxin. |
Evaluation of MALDI Biotyper Mycobacteria Library for Identification of Nontuberculous Mycobacteria.
Toney NC , Zhu W , Jensen B , Gartin J , Anderson K , Lonsway D , Karlsson M , Rasheed JK . J Clin Microbiol 2022 60 (9) e0021722 The Bruker Biotyper matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) platform was assessed on its ability to accurately identify 314 nontuberculous mycobacteria (NTM) representing 73 species. All NTM isolates, representing 183 rapidly growing and 131 slowly growing organisms, were previously identified by Sanger DNA sequencing of the full-length 16S rRNA gene, and region V of the rpoB gene. An optimized version of the Bruker bead-beating procedure for protein extraction of NTM isolates was used to ensure high quality spectra for all NTM isolates, including less frequently encountered species. NTM spectra were analyzed using Bruker's research use only, Mycobacteria Library v6.0, supplemented by the MicrobeNet database. Identification of NTM by MALDI-TOF had an accuracy of 94% (296/314). The identification accuracy for rapidly growing mycobacteria was higher at 99% (182/183) than it was for slowly growing mycobacteria at 87% (114/131). While MALDI-TOF performed well against Sanger sequencing of the 16S rRNA gene alone, there were 11 species that required additional sequencing of rpoB. Most discrepancies between MALDI-TOF and sequencing results are likely due to underrepresentation of some species in the libraries used. Overall, the results of this study support Bruker's MALDI-TOF platform as an accurate and reliable method for the identification of NTM. |
Molecular Characterization of Carbapenem-Resistant Enterobacterales Collected in the United States.
Karlsson M , Lutgring JD , Ansari U , Lawsin A , Albrecht V , McAllister G , Daniels J , Lonsway D , McKay S , Beldavs Z , Bower C , Dumyati G , Gross A , Jacob J , Janelle S , Kainer MA , Lynfield R , Phipps EC , Schutz K , Wilson L , Witwer ML , Bulens SN , Walters MS , Duffy N , Kallen AJ , Elkins CA , Rasheed JK . Microb Drug Resist 2022 28 (4) 389-397 Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (n = 349, 83%). Klebsiella pneumoniae was the most common organism (n = 265, 63%), followed by Enterobacter cloacae complex (n = 77, 18%) and Escherichia coli (n = 50, 12%). Of 419 isolates analyzed by whole genome sequencing, 307 (73%) harbored a carbapenemase gene; variants of bla(KPC) predominated (n = 299, 97%). The occurrence of carbapenemase-producing K. pneumoniae, E. cloacae complex, and E. coli varied by region; the predominant sequence type within each genus was ST258, ST171, and ST131, respectively. None of the carbapenemase-producing CRE isolates displayed resistance to all antimicrobials tested; susceptibility to amikacin and tigecycline was generally retained. |
Detection and Characterization of Targeted Carbapenem-Resistant Healthcare-Associated Threats: Findings from The Antibiotic Resistance Laboratory Network, 2017-2019.
Sabour S , Huang JY , Bhatnagar A , Gilbert SE , Karlsson M , Lonsway D , Lutgring JD , Rasheed JK , Halpin AL , Stanton RA , Gumbis S , Elkins CA , Brown AC . Antimicrob Agents Chemother 2021 65 (12) Aac0110521 Carbapenemase gene-positive (CP) Gram-negative bacilli are of significant clinical and public health concern. Their rapid detection and containment are critical to preventing their spread and additional infections they can cause. To this end, CDC developed the Antibiotic Resistance Laboratory Network (AR Lab Network), in which public health laboratories across all 50 states, several cities, and Puerto Rico characterize clinical isolates of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), and conduct colonization screens to detect the presence of mobile carbapenemase genes. In its first three years, the AR Lab Network tested 76,887 isolates and 31,001 rectal swab colonization screens. Targeted carbapenemase genes (bla(KPC), bla(NDM), bla(OXA-48-like), bla(VIM), or bla(IMP)) were detected by PCR in 35% of CRE, 2% of CRPA, <1% of CRAB, and 8% of colonization screens tested, respectively. bla(KPC) and bla(VIM) were the most common CP-CRE and CP-CRPA, respectively, but regional differences in the frequency of carbapenemase genes detected were apparent. In CRE and CRPA isolates tested for carbapenemase production and the presence of the targeted genes, 97% had concordant results; 3% of CRE and 2% of CRPA were carbapenemase production-positive but PCR-negative for those genes. Isolates harboring bla(NDM) showed the highest frequency of resistance across the carbapenems tested and those harboring bla(IMP) and bla(OXA-48-like) genes showed the lowest frequency of carbapenem resistance. The AR Lab Network provides a national snapshot of rare and emerging carbapenemase genes, delivering data to inform public health actions to limit the spread of these antibiotic resistance threats. |
Gram-negative bacteria harboring multiple carbapenemase genes, United States, 2012-2019
Ham DC , Mahon G , Bhaurla SK , Horwich-Scholefield S , Klein L , Dotson N , Rasheed JK , McAllister G , Stanton RA , Karlsson M , Lonsway D , Huang JY , Brown AC , Walters MS . Emerg Infect Dis 2021 27 (9) 2475-2479 Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation. |
Aztreonam-Avibactam Susceptibility Testing Program for Metallo-Beta-Lactamase-Producing Enterobacterales in the Antibiotic Resistance Laboratory Network, March 2019 to December 2020.
Bhatnagar A , Boyd S , Sabour S , Bodnar J , Nazarian E , Peinovich N , Wagner C , Craft B , Vagnone PS , Simpson J , Stone VN , Therrien M , Bateman A , Lower D , Huang JY , Gumbis S , Lonsway D , Lutgring JD , Karlsson M , Brown AC . Antimicrob Agents Chemother 2021 65 (8) Aac0048621 Aztreonam-avibactam is a drug combination pending phase 3 clinical trials and is suggested for treatment of severe infections caused by metallo-beta-lactamase (MBL)-producing Enterobacterales by combining ceftazidime-avibactam and aztreonam. Beginning in 2019, four Antibiotic Resistance Laboratory Network regional laboratories offered aztreonam-avibactam susceptibility testing by broth microdilution. For 64 clinical isolates tested, the MIC(50) and MIC(90) of aztreonam-avibactam were 0.5/4 μg/mL and 8/4 μg/mL, respectively. Aztreonam-avibactam displayed potent in vitro activity against the MBL-producing Enterobacterales tested. |
Acquisition of ciprofloxacin resistance among an expanding clade of β-lactamase positive, serogroup Y Neisseria meningitidis in the United States.
Potts CC , Retchless AC , McNamara LA , Marasini D , Reese N , Swint S , Hu F , Sharma S , Blain AE , Lonsway D , Karlsson M , Hariri S , Fox LM , Wang X . Clin Infect Dis 2021 73 (7) 1185-1193 BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA), have been recently reported in the USA. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011-February 2020 to identify IMD cases caused by strains with blaROB-1 or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1-containing US isolates with wild-type gyrA were identified from 2013-2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from six other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to six CCs and contained 10 unique gyrA alleles; seven were similar or identical to alleles from N. lactamica or N. gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the USA. The emerging dual-resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread. |
Infectious Period of Severe Acute Respiratory Syndrome Coronavirus 2 in 17 Nursing Home Residents-Arkansas, June-August 2020.
Surie D , Huang JY , Brown AC , Gable P , Biedron C , Gilbert SE , Garner K , Bollinger S , Gulley T , Haney T , Lyons AK , Beshearse E , Gregory CJ , Sabour S , Clemmons NS , James AE , Tamin A , Reese N , Perry-Dow KA , Brown R , Harcourt JL , Campbell D , Houston H , Chakravorty R , Paulick A , Whitaker B , Murdoch J , Spicer L , Stumpf MM , Mills L , Coughlin MM , Higdem P , Rasheed MAU , Lonsway D , Bhatnagar A , Kothari A , Anderson K , Thornburg NJ , Breaker E , Adamczyk M , McAllister GA , Halpin AL , Seely KA , Patil N , McDonald LC , Kutty PK . Open Forum Infect Dis 2021 8 (3) ofab048 BACKGROUND: To estimate the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adults with underlying conditions, we assessed duration of coronavirus disease 2019 (COVID-19) symptoms, reverse-transcription polymerase chain reaction (RT-PCR) positivity, and culture positivity among nursing home residents. METHODS: We enrolled residents within 15 days of their first positive SARS-CoV-2 test (diagnosis) at an Arkansas facility from July 7 to 15, 2020 and instead them for 42 days. Every 3 days for 21 days and then weekly, we assessed COVID-19 symptoms, collected specimens (oropharyngeal, anterior nares, and saliva), and reviewed medical charts. Blood for serology was collected on days 0, 6, 12, 21, and 42. Infectivity was defined by positive culture. Duration of culture positivity was compared with duration of COVID-19 symptoms and RT-PCR positivity. Data were summarized using measures of central tendency, frequencies, and proportions. RESULTS: We enrolled 17 of 39 (44%) eligible residents. Median participant age was 82 years (range, 58-97 years). All had ≥3 underlying conditions. Median duration of RT-PCR positivity was 22 days (interquartile range [IQR], 8-31 days) from diagnosis; median duration of symptoms was 42 days (IQR, 28-49 days). Of 9 (53%) participants with any culture-positive specimens, 1 (11%) severely immunocompromised participant remained culture-positive 19 days from diagnosis; 8 of 9 (89%) were culture-positive ≤8 days from diagnosis. Seroconversion occurred in 12 of 12 (100%) surviving participants with ≥1 blood specimen; all participants were culture-negative before seroconversion. CONCLUSIONS: Duration of infectivity was considerably shorter than duration of symptoms and RT-PCR positivity. Severe immunocompromise may prolong SARS-CoV-2 infectivity. Seroconversion indicated noninfectivity in this cohort. |
Evaluation of methods for detection of β-lactamase production in MSSA.
Skov R , Lonsway DR , Larsen J , Larsen AR , Samulioniené J , Limbago BM . J Antimicrob Chemother 2021 76 (6) 1487-1494 OBJECTIVES: Correct determination of penicillin susceptibility is pivotal for using penicillin in the treatment of Staphylococcus aureus infections. This study examines the performance of MIC determination, disc diffusion and a range of confirmatory tests for detection of penicillin susceptibility in S. aureus. METHODS: A total of 286 consecutive penicillin-susceptible S. aureus blood culture isolates as well as a challenge set of 62 MSSA isolates were investigated for the presence of the blaZ gene by PCR and subjected to penicillin-susceptibility testing using broth microdilution MIC determination, disc diffusion including reading of the zone edge, two nitrocefin tests and the cloverleaf test. RESULTS: Using PCR-based detection of blaZ as the gold standard, both broth microdilution MIC testing and disc diffusion testing resulted in a relatively low accuracy (82%-93%) with a sensitivity ranging from 49%-93%. Among the confirmatory tests, the cloverleaf test performed with 100% accuracy, while zone edge interpretation and nitrocefin-based tests increased the sensitivity of β-lactamase detection to 96%-98% and 82%-96% when using MIC determination or disc diffusion as primary test, respectively. CONCLUSIONS: This investigation showed that reliable and accurate detection of β-lactamase production in S. aureus can be obtained by MIC determination or penicillin disc diffusion followed by interpretation of the zone edge as a confirmatory test for apparently penicillin-susceptible isolates. The more cumbersome cloverleaf test can also be used. Nitrocefin-based tests should not be used as the only test for confirmation of a presumptive β-lactamase-negative isolate. |
Assessing the in vitro impact of ceftazidime on aztreonam/avibactam susceptibility testing for highly resistant MBL-producing Enterobacterales.
Bhatnagar A , Ransom EM , Machado MJ , Boyd S , Reese N , Anderson K , Lonsway D , Elkins CA , Rasheed JK , Patel JB , Karlsson M , Brown AC , Lutgring JD . J Antimicrob Chemother 2020 76 (4) 979-983 BACKGROUND: Aztreonam/avibactam is a combination agent that shows promise in treating infections caused by highly antibiotic-resistant MBL-producing Enterobacterales. This combination can be achieved by combining two FDA-approved drugs: ceftazidime/avibactam and aztreonam. It is unknown whether ceftazidime in the combination ceftazidime/aztreonam/avibactam has a synergistic or antagonistic effect on the in vitro activity of aztreonam/avibactam by significantly increasing or decreasing the MIC. OBJECTIVES: To determine whether increasing ceftazidime concentrations affect the MICs of aztreonam/avibactam alone. METHODS: A custom 8 × 8 chequerboard broth microdilution (BMD) panel was made using a digital dispenser (Hewlett-Packard, Corvallis, OR, USA). The panel included orthogonal 2-fold dilution series of aztreonam and ceftazidime ranging from 0.5 to 64 mg/L. Avibactam concentration was kept constant at 4 mg/L throughout the chequerboard. Thirty-seven Enterobacterales isolates from the CDC & FDA Antibiotic Resistance Isolate Bank or CDC's internal collection with intermediate or resistant interpretations to aztreonam and ceftazidime/avibactam were included for testing. All isolates harboured at least one of the following MBL genes: blaIMP, blaNDM or blaVIM. RESULTS: Regardless of the concentration of ceftazidime, aztreonam/avibactam with ceftazidime MICs for all 37 isolates were within one 2-fold doubling dilution of the aztreonam/avibactam MIC. CONCLUSIONS: Ceftazidime, in the combination ceftazidime/avibactam/aztreonam, did not affect the in vitro activity of aztreonam/avibactam in this sample of isolates. These findings can help assure clinical and public health laboratories that testing of aztreonam/avibactam by BMD can act as a reliable surrogate test when the combination of ceftazidime/avibactam and aztreonam is being considered for treatment of highly antibiotic-resistant MBL-producing Enterobacterales. |
Investigation of a Large Diphtheria Outbreak and Co-circulation of Corynebacterium pseudodiphtheriticum among Forcibly Displaced Myanmar Nationals, 2017-2019.
Weil LM , Williams MM , Shirin T , Lawrence M , Habib ZH , Aneke JS , Tondella ML , Zaki Q , Cassiday PK , Lonsway D , Farrque M , Hossen T , Feldstein LR , Cook N , Maldonado-Quiles G , Alam AN , Muraduzzaman AKM , Akram A , Conklin L , Doan S , Friedman M , Acosta AM , Hariri S , Fox LM , Tiwari TSP , Flora MS . J Infect Dis 2020 224 (2) 318-325 BACKGROUND: Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic Corynebacteria, such as C. pseudodiphtheriticum rarely causes diphtheria-like illness. Recently several global diphtheria outbreaks have resulted from the breakdown of healthcare infrastructures particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among Forcibly Displaced Myanmar Nationals in Bangladesh. METHODS: Specimens and clinical information were collected from patients presenting at Diphtheria Treatment Centers. Swabs were tested for toxin-gene (tox) bearing C. diphtheriae by real-time (RT) PCR and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. RESULTS: Among 382 patients; 153 (40%) tested tox-positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture-confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. CONCLUSIONS: We report the confirmation of a diphtheria outbreak and identification of a co-circulating Corynebacterium species. The high proportion of C. pseudodiphtheriticum co-detection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms. |
Detection of Ciprofloxacin-Resistant, β-Lactamase-Producing Neisseria meningitidis Serogroup Y Isolates - United States, 2019-2020.
McNamara LA , Potts C , Blain AE , Retchless AC , Reese N , Swint S , Lonsway D , Karlsson M , Lunquest K , Sweitzer JJ , Wang X , Hariri S , Fox LM . MMWR Morb Mortal Wkly Rep 2020 69 (24) 735-739 Meningococcal disease is a sudden-onset, life-threatening illness caused by the bacterium Neisseria meningitidis. Prompt empiric antibiotic treatment can reduce morbidity and mortality among patients, and antibiotic prophylaxis can prevent secondary disease in close contacts. Historically, N. meningitidis isolates in the United States have largely been susceptible to the antibiotics recommended for treatment and prophylaxis, including penicillin and ciprofloxacin. This report describes detection of penicillin-resistant and ciprofloxacin-resistant N. meningitidis serogroup Y (NmY) isolates in the United States. NmY isolates containing a blaROB-1 beta-lactamase enzyme gene conferring resistance to penicillins (1) were recovered from 33 cases reported during 2013-2020. Isolates from 11 of these cases, reported during 2019-2020, harbored a ciprofloxacin resistance-associated mutation in a chromosomal gene (gyrA). Cases were reported from 12 geographically disparate states; a majority of cases (22 of 33, 67%) occurred in Hispanic persons. These cases represent a substantial increase in penicillin-resistant and ciprofloxacin-resistant meningococci in the United States since 2013. Ceftriaxone and cefotaxime, the recommended first-line agents for empiric bacterial meningitis treatment, can continue to be used for treatment, but health care providers should ascertain susceptibility of meningococcal isolates to penicillin before switching to penicillin or ampicillin. Ongoing monitoring for antimicrobial resistance among meningococcal isolates and prophylaxis failures will be important to inform treatment and prophylaxis recommendations. |
Rapid nanopore whole-genome sequencing for anthrax emergency preparedness
McLaughlin HP , Bugrysheva JV , Conley AB , Gulvik CA , Cherney B , Kolton CB , Marston CK , Saile E , Swaney E , Lonsway D , Gargis AS , Kongphet-Tran T , Lascols C , Michel P , Villanueva J , Hoffmaster AR , Gee JE , Sue D . Emerg Infect Dis 2020 26 (2) 358-361 Human anthrax cases necessitate rapid response. We completed Bacillus anthracis nanopore whole-genome sequencing in our high-containment laboratory from a human anthrax isolate hours after receipt. The de novo assembled genome showed no evidence of known antimicrobial resistance genes or introduced plasmid(s). Same-day genomic characterization enhances public health emergency response. |
Validation of aztreonam-avibactam susceptibility testing using digitally dispensed custom panels
Ransom E , Bhatnagar A , Patel JB , Machado M , Boyd S , Reese N , Lutgring JD , Lonsway D , Anderson K , Brown AC , Elkins CA , Rasheed JK , Karlsson M . J Clin Microbiol 2020 58 (4) Aztreonam-avibactam is a combination antimicrobial agent with activity against carbapenemase-producing Enterobacteriaceae (CPE) with metallo-beta-lactamases (MbetaLs). Although aztreonam-avibactam is not yet approved by the U.S. Food and Drug Administration (FDA), clinicians can administer this combination by using two FDA-approved drugs: aztreonam and ceftazidime-avibactam. This combination of drugs is recommended by multiple experts for treatment of serious infections caused by MbetaL-producing CPE. At present, in vitro antimicrobial susceptibility testing (AST) of aztreonam-avibactam is not commercially available; thus, most clinicians receive no laboratory-based guidance that can support consideration of aztreonam-avibactam for serious CPE infections. Here, we report our internal validation for aztreonam-avibactam AST by reference broth microdilution (BMD) according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The validation was performed using custom, frozen reference BMD panels prepared in-house at the Centers for Disease Control and Prevention (CDC). In addition, we took this opportunity to evaluate a new panel-making method using a digital dispenser, the Hewlett Packard (HP) D300e. Our studies demonstrate that the performance characteristics of digitally dispensed panels were equivalent to conventionally prepared frozen reference BMD panels for a number of drugs, including aztreonam-avibactam. We found the HP D300e liquid handler to be easy-to-use and to provide the capacity to prepare complex drug panels. Our findings will assist other clinical and public health laboratories implement susceptibility testing for aztreonam-avibactam. |
Difficult-to-detect Staphylococcus aureus: mecA-positive isolates associated with oxacillin and cefoxitin false-susceptible results
Gargis AS , Yoo BB , Lonsway DR , Anderson K , Campbell D , Ewing T , Lawsin A , Machado MJ , Yamamoto N , Halpin AL , Lutgring JD , Karlsson M , Rasheed JK , Elkins CA . J Clin Microbiol 2020 58 (4) In August of 2018, the United States Food and Drug Administration (FDA) announced a Class I recall associated with a methicillin-resistant Staphylococcus aureus (MRSA) Safety Alert. |
Partnerships involved in public health testing for Zika virus in Florida, 2016
Heberlein-Larson L , Gillis LD , Morrison A , Scott B , Cook M , Cannons A , Quaye E , White S , Cone M , Mock V , Schiffer J , Lonsway D , Petway M , Otis A , Stanek D , Hamilton J , Crowe S . Public Health Rep 2019 134 43s-52s The emergence of Zika virus in the Americas in 2015 and its association with birth defects and other adverse health outcomes triggered an unprecedented public health response and a demand for testing. In 2016, when Florida exceeded state public health laboratory capacity for diagnostic testing, the state formed partnerships with federal and commercial laboratories. Eighty-two percent of the testing (n = 33 802 of 41 008 specimens) by the laboratory partners, including Florida's Bureau of Public Health Laboratories (BPHL; n = 13 074), a commercial laboratory (n = 19 214), and the Centers for Disease Control and Prevention (CDC; n = 1514), occurred from July through November 2016, encompassing the peak period of local transmission. These partnerships allowed BPHL to maintain acceptable test turnaround times of 1 to 4 days for nucleic acid testing and 3 to 7 days for serologic testing. Lessons learned from this response to inform future outbreaks included the need for early planning to establish outside partnerships, adding specimen triage strategies to surge plans, and integrating state and CDC information systems. |
Correlation between Etest and reference broth microdilution for antimicrobial susceptibility testing of Burkholderia pseudomallei
Lonsway DR , Elrod MG , Kendrick N , Tiller R , Sullivan MM , Edwards JR , Blaney DD , Karlsson M . Microb Drug Resist 2019 26 (4) 311-318 A three-center study was performed to see if Etest gradient diffusion minimum inhibitory concentration (MIC) methodology correlated with reference broth microdilution (BMD) for antimicrobial susceptibility testing of Burkholderia pseudomallei against six antimicrobial agents known to be usually effective against B. pseudomallei. This study was performed to assist in the decision-making process for possible deployment of the Etest method for antimicrobial susceptibility testing of B. pseudomallei into several regional public health laboratories in the United States. Three laboratories each tested a challenge set of 30 genotypically diverse isolates collected from 15 different countries. MICs were performed by both Etest gradient diffusion and reference BMD for amoxicillin/clavulanate, ceftazidime, doxycycline, imipenem, tetracycline, and trimethoprim/sulfamethoxazole. Etest results for amoxicillin/clavulanate, ceftazidime, doxycycline, and imipenem correlated well with reference BMD by both category interpretation (>/=97%) and essential agreement of MIC (>/=93%). Tetracycline and trimethoprim/sulfamethoxazole Etests yielded poor correlation with BMD by category interpretation (80%) and essential agreement (70%), respectively. In conclusion, Etest gradient diffusion represents a valid option for antimicrobial susceptibility testing of B. pseudomallei against amoxicillin/clavulanate, ceftazidime, doxycycline, and imipenem. Tetracycline and trimethoprim/sulfamethoxazole Etest results showed some concerning lack of correlation with the corresponding reference BMD results. |
Conjugal Transfer, Whole Genome Sequencing, and Plasmid Analysis of Four mcr-1 -bearing Isolates from U.S. Patients.
Zhu W , Lawsin A , Lindsey RL , Batra D , Knipe K , Yoo BB , Perry KA , Rowe LA , Lonsway D , Waters MS , Rasheed JK , Halpin AL . Antimicrob Agents Chemother 2019 63 (4) Four Enterobacteriaceae clinical isolates bearing mcr-1 gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to E. coli; plasmids were stable in conjugants after multiple passages on non-selective media. mcr-1 was located on an IncX4 (n=3) or IncN (n=1) plasmid. The IncN plasmid harbored 13 additional antimicrobial resistance genes. Results indicate the mcr-1-bearing plasmids in this study are highly transferable in vitro and stable in the recipients. |
Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope.
Shenoy ES , Pierce VM , Walters MS , Moulton-Meissner H , Lawsin A , Lonsway D , Shugart A , McAllister G , Halpin AL , Zambrano-Gonzalez A , Ryan EE , Suslak D , DeJesus A , Barton K , Madoff LC , McHale E , DeMaria A , Hooper DC . Clin Infect Dis 2018 68 (8) 1327-1334 Background: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. Methods: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. Results: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. K. pneumoniae and E. coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. Conclusions: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of an FDA-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings. |
Hospital microbiology laboratory practices for Enterobacteriaceae: Centers for Disease Control and Prevention National Healthcare Safety Network (NHSN) annual survey, 2015 and 2016
Shugart A , Walters MS , Weiner LM , Lonsway D , Kallen AJ . Infect Control Hosp Epidemiol 2018 39 (9) 1-3 We analyzed clinical microbiology laboratory practices for detection of multidrug-resistant Enterobacteriaceae in US short-stay acute-care hospitals using data from the National Healthcare Safety Network (NHSN) Annual Facility Survey. Half of hospitals reported testing for carbapenemases, and 1% performed routine polymyxin susceptibility testing using reference broth microdilution. |
Notes from the Field: Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae from Less Common Enterobacteriaceae Genera - United States, 2014-2017
Walters MS , Witwer M , Lee YK , Albrecht V , Lonsway D , Rasheed JK , Anacker M , Snippes-Vagnone P , Lynfield R , Kallen AJ . MMWR Morb Mortal Wkly Rep 2018 67 (23) 668-669 Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are associated with high mortality rates (1). Carbapenemases encoded on plasmids can move between bacterial strains and have the potential to rapidly increase the proportion of Enterobacteriaceae resistant to carbapenems; as such, CP-CRE have been a particular focus of public health response. Although the Enterobacteriaceae family includes approximately 50 recognized genera, surveillance for CP-CRE has focused on the organisms most associated with clinical infections: Klebsiella spp., Enterobacter spp., and Escherichia coli (2,3). CRE from other, less commonly encountered genera (hereafter referred to as less common genera) have generally not been targeted for carbapenemase testing, in part, because some of these organisms possess intrinsic resistance to the carbapenem imipenem and others express species-specific chromosomal carbapenemases. However, these organisms can also harbor plasmid-mediated carbapenemases. This report describes CP-CRE from less common genera identified through reference testing at CDC and surveillance at the Minnesota Department of Health (MDH) Public Health Laboratory. |
Phenotypic and Genotypic Characterization of Enterobacteriaceae Producing Oxacillinase-48-Like Carbapenemases, United States.
Lutgring JD , Zhu W , de Man TJB , Avillan JJ , Anderson KF , Lonsway DR , Rowe LA , Batra D , Rasheed JK , Limbago BM . Emerg Infect Dis 2018 24 (4) 700-709 Oxacillinase (OXA)-48-like carbapenemases remain relatively uncommon in the United States. We performed phenotypic and genotypic characterization of 30 Enterobacteriaceae producing OXA-48-like carbapenemases that were recovered from patients during 2010-2014. Isolates were collected from 12 states and not associated with outbreaks, although we could not exclude limited local transmission. The alleles beta-lactamase OXA-181 (blaOXA-181) (43%), blaOXA-232 (33%), and blaOXA-48 (23%) were found. All isolates were resistant to ertapenem and showed positive results for the ertapenem and meropenem modified Hodge test and the modified carbapenem inactivation method; 73% showed a positive result for the Carba Nordmann-Poirel test. Whole-genome sequencing identified extended-spectrum beta-lactamase genes in 93% of isolates. In all blaOXA-232 isolates, the gene was on a ColKP3 plasmid. A total of 12 of 13 isolates harboring blaOXA-181 contained the insertion sequence DeltaISEcp1. In all isolates with blaOXA-48, the gene was located on a TN1999 transposon; these isolates also carried IncL/M plasmids. |
Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae , United States 2016.
de Man TJB , Lutgring JD , Lonsway DR , Anderson KF , Kiehlbauch JA , Chen L , Walters MS , Sjolund-Karlsson M , Rasheed JK , Kallen A , Halpin AL . mBio 2018 9 (2) Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. PATIENT: The isolate harbored four known beta-lactamase genes, including plasmid-mediated blaNDM-1 and blaCMY-6, as well as chromosomal blaCTX-M-15 and blaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. PATIENT: Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread. |
Multicenter Evaluation of the Modified Carbapenem Inactivation Method and the Carba NP for Detection of Carbapenemase-Producing Pseudomonas aeruginosa and Acinetobacter baumannii.
Simner PJ , Johnson JK , Brasso WB , Anderson K , Lonsway DR , Pierce VM , Bobenchik AM , Lockett ZC , Charnot-Katsikas A , Westblade LF , Yoo BB , Jenkins SG , Limbago BM , Das S , Roe-Carpenter DE . J Clin Microbiol 2017 56 (1) The purpose of this study was to develop the modified Carbapenem Inactivation Method (mCIM) for the detection of carbapenemase-producing (CP) Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) and perform a multicenter evaluation of the mCIM and Carba NP tests for these non-fermenters. Thirty P. aeruginosa and 30 A. baumannii isolates previously characterized by whole genome sequencing from the CDC-FDA Antibiotic Resistance Isolate Bank were evaluated, including carbapenemase-producers (CP; Ambler Class A, B, and D), non-carbapenemase-producing (non-CP) carbapenem-resistant isolates, and carbapenem-susceptible isolates. Initial comparison of a 1 microl versus 10 microl loop inoculum for the mCIM was performed by two testing sites and showed that 10 microl was required for reliable detection of carbapenemase production among PA and AB. Ten testing sites then evaluated the mCIM using a 10 microl loop inoculum. Overall, the mean sensitivity and specificity of the mCIM for detection of CP-PA across all ten sites were 98.0% (95% CI: 94.3-99.6; range: 86.7-100) and 95% (95% CI: 89.8-97.7; range: 93.3-100), whereas the mean sensitivity and specificity among CP-AB were 79.8% (95% CI: 74.0-84.9; range: 36.3-95.7) and 52.9% (95% CI: 40.6- 64.9; range: 28.6-100), respectively. At three sites that evaluated the performance of the Carba NP using the same set of isolates, the mean sensitivity and specificity of the Carba NP were 97.8% (95% CI: 88.2-99.9; range: 93.3-100) and 97.8% (95% CI: 88.2-99.9; range: 93.3-100) for PA and 18.8% (95%CI: 10.4-30.1; range: 8.7-26.1) and 100% (95% CI: 83.9-100; range: 100) for AB. Overall, we found both the mCIM and the Carba NP to be accurate for detection of carbapenemases among PA and less reliable for use with AB isolates. |
Modified Carbapenem Inactivation Method for Phenotypic Detection of Carbapenemase Production among Enterobacteriaceae
Pierce VM , Simner PJ , Lonsway DR , Roe-Carpenter DE , Johnson JK , Brasso WB , Bobenchik AM , Lockett ZC , Charnot-Katsikas A , Ferraro MJ , Thomson RB Jr , Jenkins SG , Limbago BM , Das S . J Clin Microbiol 2017 55 (8) 2321-2333 The ability of clinical microbiology laboratories to reliably detect carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) is an important element of the effort to prevent and contain the spread of these pathogens and an integral part of antimicrobial stewardship. Existing methods each have limitations. A new, straightforward, inexpensive, and specific phenotypic method for the detection of carbapenemase production, the carbapenem inactivation method (CIM), was recently described. Here we describe a two-stage evaluation of a modified carbapenem inactivation method (mCIM), in which tryptic soy broth was substituted for water during the inactivation step and the length of this incubation was extended. A validation study was performed in a single clinical laboratory to determine the accuracy of the mCIM, followed by a nine-laboratory study to verify the reproducibility of these results and define the zone size cut-off that best discriminated between CP-CRE and Enterobacteriaceae that do not produce carbapenemases. Bacterial isolates previously characterized through whole genome sequencing or targeted PCR as to the presence or absence of carbapenemase genes were tested for carbapenemase production using the mCIM; isolates with Ambler class A, B, and D carbapenemases, non-CP-CRE isolates, and carbapenem-susceptible isolates were included. The sensitivity of the mCIM observed in the validation study was 99% (95% confidence interval [CI], 93 to 100) and the specificity was 100% (95% CI, 82 to 100). In the second stage of the study, the range of sensitivities observed across nine laboratories was 93% to 100%, with a mean of 97%; the range of specificities was 97% to 100%, with a mean of 99%. The mCIM was easy to perform and interpret for Enterobacteriaceae, with results in less than 24 hours and excellent reproducibility across laboratories. |
Investigation of First Identified mcr-1 Gene in an Isolate from a U.S. Patient - Pennsylvania, 2016.
Kline KE , Shover J , Kallen AJ , Lonsway DR , Watkins S , Miller JR . MMWR Morb Mortal Wkly Rep 2016 65 (36) 977-978 In 2015, scientists reported the emergence of the plasmid-encoded mcr-1 gene conferring bacterial resistance to the antibiotic colistin (1), signaling potential emergence of a pandrug-resistant bacterium. In May 2016, mcr-1-positive Escherichia coli was first isolated from a specimen from a U.S. patient (2) when a Pennsylvania woman was evaluated for a urinary tract infection. The urine culture and subsequent testing identified the gene in an extended-spectrum beta-lactamase (ESBL)-producing E. coli with reduced susceptibility to colistin. The patient had no international travel for approximately 1 year, no livestock exposure, and a limited role in meal preparation with store-bought groceries; however, she had multiple and repeated admissions to four medical facilities during 2016. |
Evaluation of an immunochromatographic assay for rapid detection of penicillin-binding protein 2a in human and animal Staphylococcus intermedius group, Staphylococcus lugdunensis, and Staphylococcus schleiferi clinical isolates
Arnold AR , Burham CD , Ford BA , Lawhon SD , McAllister SK , Lonsway D , Albrecht V , Jerris RC , Rasheed JK , Limbago B , Burd EM , Westblade LF . J Clin Microbiol 2015 54 (3) 745-8 The performance of a rapid penicillin-binding protein 2a (PBP2a) detection assay, the Alere PBP2a Culture Colony Test, was evaluated for identification of PBP2a-mediated beta-lactam resistance in human and animal clinical isolates of Staphylococcus intermedius group, Staphylococcus lugdunensis, and Staphylococcus schleiferi. The assay was sensitive and specific, with all PBP2a-negative and -positive strains testing negative and positive, respectively. |
Notes from the field: Carbapenem-resistant Enterobacteriaceae producing OXA-48-like carbapenemases - United States, 2010-2015
Lyman M , Walters M , Lonsway D , Rasheed K , Limbago B , Kallen A . MMWR Morb Mortal Wkly Rep 2015 64 (47) 1315-6 Carbapenem-resistant Enterobacteriaceae (CRE) are bacteria that are often resistant to most classes of antibiotics and cause health care-associated infections with high mortality rates Among CRE, strains that carry plasmid-encoded carbapenemase enzymes that inactivate carbapenem antibiotics are of greatest public health concern because of their potential for rapid global dissemination, as evidenced by the increasing distribution of CRE that produce the Klebsiella pneumoniae carbapenemase and the New Delhi metallo-beta-lactamase. Newly described resistance in Enterobacteriaceae, such as plasmid-mediated resistance to the last-line antimicrobial colistin, recently detected in China, and resistance to the newly approved antimicrobial, ceftazidime-avibactam, identified from a U.S. K. pneumoniae carbapenemase-producing isolate, highlight the continued urgency to delay spread of CRE. Monitoring the emergence of carbapenemases is crucial to limiting their spread; identification of patients carrying carbapenemase-producing CRE should result in the institution of transmission-based precautions and enhanced environmental cleaning to prevent transmission. The OXA-48 carbapenemase was first identified in Enterobacteriaceae in Turkey in 2001, and OXA-48-like variants have subsequently been reported around the world. The first U.S. reports of OXA-48-like carbapenemases were published in 2013 and included retrospectively identified isolates from 2009 and two isolates collected in 2012 from patients in Virginia who had recently been hospitalized outside the United States. Although there are limited additional published reports from the United States, CDC continues to receive reports of these organisms. This report describes patients identified as carrying CRE producing OXA-48-like carbapenemases in the United States during June 2010-August 2015. |
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