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 ◽  
...  

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.

2020 ◽  
Vol 41 (S1) ◽  
pp. s149-s150
Author(s):  
Jennifer Huang ◽  
Amanda Pettinger ◽  
Katie Bantle ◽  
Amelia Bhatnagar ◽  
Sarah Gilbert ◽  
...  

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant morbidity and mortality each year in the United States. Treatment options for these infections are often limited, in part due to carbapenemases, which are mobile β-lactam-hydrolyzing enzymes that confer multidrug resistance in CRE. As part of the CDC’s Containment Strategy for Emerging Resistance, public health laboratories (PHLs) in the CDC Antibiotic Resistance Laboratory Network (AR Lab Network) have worked to characterize clinical isolates of CRE for rapid identification of carbapenemase genes. These data are then used by public health and healthcare partners to promote patient safety by decreasing the spread of resistance. We summarize carbapenemase gene profiles in CRE, by genus and geography, using data collected through the AR Lab Network from January 2018 through August 2019. Methods: CRE isolates were submitted to 55 PHLs, including those of all 50 states, 4 large cities, and Puerto Rico, in accordance with each jurisdiction’s reporting laws. PHLs performed phenotypic and molecular testing on isolates to detect targeted, emerging carbapenemase genes and reported results to submitters. Carbapenemase-positive (CP) isolates were defined as PCR positive for ≥1 carbapenemase gene tested: blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48–LIKE. PHLs submitted results to CDC monthly. Genera other than Enterobacter, Klebsiella, and Escherichia coli are categorized as other genera in this analysis. Data were compiled and analyzed using SAS v 9.4 software. Results: From January 2018 to August 2019, the AR Lab Network tested 25,705 CRE isolates; 8,864 of 25,705 CRE (34%) were CP. Klebsiella spp represented the largest proportion of CP-CRE at 68% (n = 6,063), followed by E. coli (12%, n = 1,052), Enterobacter spp (11%, n = 981), and other genera (9%, n = 768). Figure 1a shows the composition of CP-CRE carbapenemase genes by genus. The most common carbapenemase and genus profiles were blaKPC in Klebsiella (74%; 5,562 of 7,561 blaKPC-positive) blaNDM in E. coli (43%; 372 of 868 blaNDM-positive) blaVIM in Enterobacter spp (35%; 25 of 72 blaVIM-positive), and blaIMP among other genera (90%; 92 of 102 blaIMP-positive). Common CP-CRE genes and genera also varied by geography (Fig. 1b). Conclusions: The AR Lab Network has greatly enhanced our nation’s ability to detect and characterize CP-CRE. Our data provide a snapshot of the organisms and regions where mobile carbapenemase genes are most often detected in CRE. Geographic variation in CP gene profiles provides actionable data to inform local priorities for detection and infection control and provide clinicians with situational awareness of the genes and organisms that are circulating in their region.Funding: NoneDisclosures: In this presentation, the authors discuss the drug combination aztreonam-avibactam and acknowledge that this drug combination is not currently FDA-approved.


Author(s):  
Snigdha Vallabhaneni ◽  
Jennifer Y. Huang ◽  
Julian E. Grass ◽  
Amelia Bhatnagar ◽  
Sarah Sabour ◽  
...  

Background: Detection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) with carbapenamase-producing (CP) genes is critical for preventing transmission. Our objective was to assess whether certain antimicrobial susceptibility testing (AST) profiles can efficiently identify CP-CRPA. Methods: We defined CRPA as P. aeruginosa with imipenem or meropenem MICs of ≥8μg/ml; CP-CRPA were CRPA with CP genes (blaKPC/blaIMP/blaNDM/blaVIM). We assessed the sensitivity and specificity of AST profiles to detect CP-CRPA among CRPA collected by CDC’s Antibiotic Resistance Laboratory Network (AR Lab Network) and the Emerging Infections Program (EIP) during 2017–2019. Results: Three percent (195/6192) of AR Lab Network CRPA were CP-CRPA. Among CRPA, adding not susceptible (NS) to cefepime or ceftazidime to the definition had 91% sensitivity and 50% specificity for identifying CP-CRPA; NS to ceftolozane-tazobactam had 100% sensitivity and 86% specificity. Of 965 EIP CRPA evaluated for CP genes, seven CP-CRPA were identified; 6 of 7 were NS to cefepime and ceftazidime, and all 7 were NS to ceftolozane-tazobactam. Among 4182 EIP isolates, clinical laboratory AST results were available for 96% for cefepime, 80% for ceftazidime, and 4% for ceftolozane-tazobactam. The number of CRPA needed to test (NNT) to identify one CP-CRPA decreased from 138 to 64 if the definition of NS to cefepime or ceftazidime was used and to 7 with NS to ceftolozane-tazobactam. Conclusion: Adding not susceptible to cefepime or ceftazidime to CRPA carbapenemase testing criteria would reduce the NNT by half and can be implemented in most clinical laboratories; adding not susceptible to ceftolozane-tazobactam could be even more predictive once AST for this drug is more widely available.


Author(s):  
Christian M Gill ◽  
Elif Aktaþ ◽  
Wadha Alfouzan ◽  
Lori Bourassa ◽  
Adrian Brink ◽  
...  

Abstract Background Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are a global challenge. However, detection efforts can be laborious because numerous mechanisms produce carbapenem resistance. An MIC based algorithm (imipenem or meropenem-resistant plus ceftazidime-non-susceptible plus cefepime-non-susceptible) was proposed to identify isolates most likely to harbor a carbapenemase; however, prospective validation in geographies displaying genotypic diversity and varied carbapenemase prevalence is warranted. Methods CRPA were collected during the ERACE-PA global surveillance program from 17 sites in 12 countries. Isolates underwent susceptibility testing following local standards to ceftazidime, cefepime, and ceftolozane/tazobactam. Isolates underwent initial phenotypic carbapenemase screening followed by molecular testing if positive. The primary algorithm criteria were applied and results compared to phenotypic carbapenemase results to assess the performance of the algorithm. A secondary criteria of (the algorithm criteria or imipenem or meropenem-resistant plus ceftolozane/tazobactam-non-susceptible) was assessed. Results 807 CRPA were assessed and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by GES. Addition of the criteria of imipenem or meropenem-resistant plus ceftolozane/tazobactam-non-susceptible decreased the number of CP-CRPA missed by the algorithm (21 versus 40 isolates, respectively) still reducing number of isolates tested by 39%. Conclusions Application of the initial algorithm (imipenem or meropenem-resistant plus ceftazidime-non-susceptible plus cefepime-non-susceptible) performed well in a global cohort with 33% phenotypically carbapenemase-positive isolates. Addition of imipenem or meropenem-resistant plus ceftolozane/tazobactam-non-susceptible reduced the number of phenotypically carbapenemase-positive isolates missed and may be useful in areas with a prominence of GES.


2020 ◽  
Vol 41 (S1) ◽  
pp. s474-s476
Author(s):  
Julian E. Grass ◽  
Shelley S. Magill ◽  
Isaac See ◽  
Uzma Ansari ◽  
Lucy E. Wilson ◽  
...  

Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.Funding: NoneDisclosures: None


2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Michael J. Satlin ◽  
Liang Chen ◽  
Gopi Patel ◽  
Angela Gomez-Simmonds ◽  
Gregory Weston ◽  
...  

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.


1999 ◽  
Vol 123 (4) ◽  
pp. 285-289 ◽  
Author(s):  
Gary V. Doern ◽  
Angela B. Brueggemann ◽  
Michael A. Pfaller ◽  
Ronald N. Jones

Abstract Objective.—To assess the performance of clinical microbiology laboratories in the United States when conducting in vitro susceptibility tests with Streptococcus pneumoniae. Methods.—The results of a nationwide College of American Pathologists Proficiency Survey test sample, in which susceptibility testing of an isolate of S pneumoniae was performed, were assessed with respect to precision and accuracy. Results.—Wide variability was noted among participating laboratories with both minimum inhibitory concentration procedures and disk diffusion susceptibility tests when both methods were applied to S pneumoniae. Despite this high degree of variation, categorical interpretive errors were uncommon. Numerous laboratories reported results for antimicrobial agents that are not recommended by the National Committee for Clinical Laboratory Standards for tests with S pneumoniae. Conclusions.—Current susceptibility testing practices with S pneumoniae in the United States indicate limited precision and a tendency for laboratories to test and report results obtained with antimicrobial agents of questionable therapeutic value against this organism. Continued efforts to standardize susceptibility testing of S pneumoniae in the United States are warranted. In addition, modifications of existing interpretive criteria may be necessary.


2006 ◽  
Vol 50 (9) ◽  
pp. 2941-2945 ◽  
Author(s):  
Karen Lolans ◽  
Thomas W. Rice ◽  
L. Silvia Munoz-Price ◽  
John P. Quinn

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified bla OXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a bla OXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Garima Bansal ◽  
Rachelle Allen-McFarlane ◽  
Broderick Eribo

The occurrence of carbapenem-resistant (CR) strains of Acinetobacter baumannii is reported to contribute to the severity of several nosocomial infections, especially in critically ill patients in intensive care units. The present study aims to determine the antibiotic susceptibility, clonality, and genetic mechanism of carbapenem resistance in twenty-eight Acinetobacter baumannii isolates from four hospitals in Washington DC. The antibiotic susceptibility of the isolates was determined by VITEK 2 analyses, while PCR was used to examine the presence of antibiotic-resistant genes and mobile genetic elements. Trilocus multiplex-PCR was used along with pulsed-field gel electrophoresis (PFGE) for strain typing and for accessing clonal relationships among the isolates. Antimicrobial susceptibility testing indicated that 46% of the isolates were carbapenem-resistant and possessed MDR and XDR phenotypes. PFGE clustered the 28 isolates into seven clonal (C1–C7) complexes based on >75% similarity cut-off. Thirty-six percent of the isolates belonged to international clone II, while 29% were assigned to Group 4 by trilocus multiplex-PCR. Although the blaOXA-51-like gene was found in all the isolates, only 36% were positive for the blaOXA-23-like gene. PCR analysis also found a metallo-β-lactamase (MBL) gene (blaVIM) in 71% of the isolates. Of the 13 CR isolates, 8 were PCR positive for both blaVIM and blaOXA-23-like genes, while 5 harbored only blaVIM gene. This study revealed the emergence of VIM carbapenemase-producing A. baumannii isolates, which has not been previously reported in the United States.


2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Brian H. Harcourt ◽  
Raydel D. Anderson ◽  
Henry M. Wu ◽  
Amanda C. Cohn ◽  
Jessica R. MacNeil ◽  
...  

Abstract Background.  Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. Methods.  Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. Results.  All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008–16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. Conclusions.  Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use.


2019 ◽  
Vol 57 (7) ◽  
Author(s):  
Tam T. Van ◽  
Emi Minejima ◽  
Chiao An Chiu ◽  
Susan M. Butler-Wu

ABSTRACT Fluoroquinolones remain some of the more commonly prescribed antimicrobial agents in the United States, despite the wide array of reported side effects that are associated with their use. In 2019, the Clinical and Laboratory Standards Institute revised the fluoroquinolone antimicrobial susceptibility testing breakpoints for both Enterobacteriaceae and Pseudomonas aeruginosa. This breakpoint revision was deemed necessary on the basis of pharmacokinetic and pharmacodynamic analyses suggesting that the previous breakpoints were too high, in addition to the inability of the previous breakpoints to detect low-level resistance to this antibiotic class. In this minireview, we review the published data in support of this revision, as well as the potential challenges that these breakpoint revisions are likely to pose for clinical laboratories.


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