scholarly journals Prevalence of Invasive Infections Due to Carbapenem-Resistant Enterobacteriaceae among Adult Patients in U.S. Hospitals

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Thomas Lodise ◽  
Michael J. Ye ◽  
Qi Zhao
Keyword(s):  
Large Scale ◽  
Geographic Region ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Support Tools ◽  
Invasive Infections ◽  
Risk Patients ◽  
Inpatient Database ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Ongoing Monitoring

ABSTRACT This large-scale retrospective analysis (n = 60,551) of the Premier inpatient database (1 January 2011 to 31 December 2014) found an overall prevalence of carbapenem-resistant Enterobacteriaceae strains of 2.3% (range, 0.9% to 5.8% by geographic region) among patients with infections due to Enterobacteriaceae. Ongoing monitoring and development of decision support tools/algorithms are needed for identification of high-risk patients.

scholarly journals Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae

2016 ◽  
Vol 60 (10) ◽  
pp. 6425-6429 ◽  
Author(s):  
Pranita D. Tamma ◽  
Yanjie Huang ◽  
Belita N. A. Opene ◽  
Patricia J. Simner
Keyword(s):  
Infection Control ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Rapid Spread ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACTCarbapenemase-producing (CP)Enterobacteriaceaeare largely responsible for the rapid spread of carbapenem-resistantEnterobacteriaceae(CRE). Distinguishing CP-CRE from non-CP-CRE has important infection control implications. In a cohort of 198 CRE isolates, for isolates that remained susceptible or intermediate to some carbapenem antibiotics, an ertapenem MIC of 0.5 μg/ml and meropenem, imipenem, and doripenem MICs of 2 μg/ml were best able to distinguish CP-CRE from non-CP-CRE isolates.

scholarly journals Insights into the Unique Nature of the East Asian Clade of the Emerging Pathogenic Yeast Candida auris

2019 ◽  
Vol 57 (4) ◽  
Author(s):  
Rory M. Welsh ◽  
D. Joseph Sexton ◽  
Kaitlin Forsberg ◽  
Snigdha Vallabhaneni ◽  
Anastasia Litvintseva
Keyword(s):  
Large Scale ◽  
East Asian ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type ◽  
New Information ◽  
Asian Clade ◽  
Single Region ◽  
Invasive Infections ◽  
Unique Nature

ABSTRACT The emerging yeast Candida auris can be highly drug resistant, causing invasive infections, and large outbreaks. C. auris went from an unknown pathogen a decade ago to being reported in over thirty countries on six continents. C. auris consists of four discrete clades, based on where the first isolates of the clade were reported, South Asian (clade I), East Asian (clade II), African (clade III), and South American (clade IV). These clades have unique genetic and biochemical characteristics that are important to understand and inform the global response to C. auris. Clade II has been underrepresented in the literature despite being the first one discovered. In this issue of the Journal of Clinical Microbiology, Y. J. Kwon et al. (J Clin Microbiol 57:e01624-18, 2019, https://doi.org/10.1128/JCM.01624-18) describe the largest collection of clinical isolates from Clade II, which is also the longest-running span of clinical cases, 20 years, from any single region to date. Clade II appears to have a propensity for the ear that is uncharacteristic of the other clades, which typically cause invasive infections and large-scale outbreaks. This study provides new information on an understudied lineage of C. auris and has important implications for future surveillance.

scholarly journals Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-ProducingEnterobacteriaceae

2018 ◽  
Vol 31 (2) ◽  
Author(s):  
Jesús Rodríguez-Baño ◽  
Belén Gutiérrez-Gutiérrez ◽  
Isabel Machuca ◽  
Alvaro Pascual
Keyword(s):  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Beta Lactamase ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
Development Of Resistance ◽  
Extended Spectrum ◽  
Invasive Infections ◽  
Risk Patients

SUMMARYTherapy of invasive infections due to multidrug-resistantEnterobacteriaceae(MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam–β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producingEnterobacteriaceae(CPE), only some “second-line” drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.

scholarly journals Estimating the Size of the U.S. Market for New Antibiotics with Activity against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Cornelius J. Clancy ◽  
M. Hong Nguyen
Keyword(s):  
United States ◽  
The United States ◽  
Content Type ◽  
Antibiotic Development ◽  
Development Models ◽  
Carbapenem Resistant ◽  
Financial Difficulties ◽  
New Antibiotics ◽  
The U.S ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT New antibiotics with activity against carbapenem-resistant Enterobacteriaceae (CRE) improve outcomes of CRE-infected patients. However, companies developing these drugs have faced financial difficulties. Sales of ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin in the United States totaled $101 million from February 2018 to January 2019. We estimate that the current annual U.S. market for new anti-CRE antibiotics is $289 million (range, $169 to $439 million). Without new antibiotic development models and/or reimbursement reform, the majority of anti-CRE drugs will be commercially inviable.

scholarly journals Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
Thomas Nolan ◽  
Jonathan Parkinson ◽  
Debora Rubio-Aparicio ◽  
...  
Keyword(s):  
Body Weight ◽  
Lung Infection ◽  
Infection Model ◽  
Bacterial Killing ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Infection Models ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae. The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.

scholarly journals Unusual Escherichia coli PBP 3 Insertion Sequence Identified from a Collection of Carbapenem-Resistant Enterobacteriaceae Tested In Vitro with a Combination of Ceftazidime-, Ceftaroline-, or Aztreonam-Avibactam

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Yunliang Zhang ◽  
Ankita Kashikar ◽  
C. Adam Brown ◽  
Gerald Denys ◽  
Karen Bush
Keyword(s):  
Escherichia Coli ◽  
Health Care ◽  
Gene Duplication ◽  
Insertion Sequence ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Health Care Centers ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam), and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one Escherichia coli isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP 3) as the result of gene duplication.

scholarly journals Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
William R. Wilson ◽  
Ellen G. Kline ◽  
Chelsea E. Jones ◽  
Kristin T. Morder ◽  
Roberta T. Mettus ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Strip Testing ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We describe the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered Escherichia coli isolates harboring mutant blaKPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam MICs were 1 and 0.03 µg/ml, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MICs ≤ 4 µg/ml). Against Klebsiella pneumoniae isolates harboring mutant blaKPC, the addition of vaborbactam lowered the meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates with mutant ompK36 porin genes (n = 26) than against those with wild-type ompK36 porin genes (n = 54) (0.25 versus 0.03 µg/ml; P < 0.0001). Against E. coli TOP10 isolates with plasmid constructs containing wild-type blaKPC or mutant blaKPC, the addition of vaborbactam at 8 µg/ml lowered the meropenem MICs 2- to 512-fold, resulting in meropenem-vaborbactam MICs of 0.03 µg/ml. The rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged from 90 to 95%. Essential agreement rates were higher for research-use-only (RUO) gradient strips manufactured by bioMérieux (82%) than for those manufactured by Liofilchem (48%) (P < 0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae isolates with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36. The results of susceptibility testing with RUO bioMérieux gradient strips most closely aligned with those of broth microdilution methods.

scholarly journals Comparison of 30- and 90-Day Mortality Rates in Patients with Cultures Positive for Carbapenem-resistant Enterobacteriaceae and Acinetobacter in Atlanta, 2011–2015

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S44-S44
Author(s):  
Mary Elizabeth Sexton ◽  
Chris Bower ◽  
Stephen Sukumaran ◽  
Jesse T Jacob
Keyword(s):  
Survival Analysis ◽  
Acinetobacter Baumannii ◽  
Mortality Rates ◽  
Vital Statistics ◽  
Rank Test ◽  
Invasive Infection ◽  
Emerging Infections ◽  
Carbapenem Resistant ◽  
Invasive Infections ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) and Acinetobacter baumannii (CRAB) pose a threat to public health, but comparisons of disease burden are limited. We compared survival in patients following cultures positive for CRE or CRAB. Methods The Georgia Emerging Infections Program performs active population-based and laboratory-based surveillance for CRE and CRAB in metropolitan Atlanta, GA. Using standard CDC definitions, we included patients who had incident carbapenem-nonsusceptible E. coli, Klebsiella spp., Enterobacter spp., or Acinetobacter baumannii isolated from urine only (noninvasive infection) or a sterile site (invasive infection) between 8/2011 and 12/2015. Death dates, verified by Georgia Vital Statistics records, were used to calculate 30- and 90-day mortality rates. We used the chi-square test for mortality rates and the log-rank test for survival analysis to 90 days to compare patients with invasive CRAB, noninvasive CRAB, invasive CRE, and noninvasive CRE. Results There were 535 patients with CRE (87 invasive, 448 noninvasive) and 279 (78 invasive, 201 noninvasive) with CRAB. Nearly all patients with CRE and CRAB had healthcare exposures (97.2% vs. 100%) and most were immunosuppressed (62.6% vs. 56.3%). Both 30-day (24.4% vs. 18.3%, p = 0.04) and 90-day (37.6% vs. 30.5%, p = 0.04) mortality were higher in patients with CRAB than CRE. Patients with invasive infections were more likely to die at 90 days than those with noninvasive infections (53.3% vs. 38.4%, p &lt; 0.0001). Overall mortality rates for invasive infection were similar between CRAB and CRE at 30 (44.9% vs. 34.5% p = 0.2) and 90 days (59.0% vs. 48.3%, p = 0.2). Using survival analysis at 90 days, invasive CRAB had the worst outcomes, followed by invasive CRE, noninvasive CRAB and noninvasive CRE &#x2028;(p &lt; 0.0001, see Figure). Conclusion Ninety -day mortality for invasive infections with CRE and CRAB was ~50%, and patients with CRAB had lower survival than those with CRE, suggesting that prevention efforts may need to prioritize CRAB as highly as CRE in facilities with endemic CRAB. With the high proportion of healthcare exposures and immunosuppression, these infections may signify poor prognosis or directly contribute to mortality. Disclosures All authors: No reported disclosures.

scholarly journals The Times They Are a-Changin': Carbapenems for Extended-Spectrum-β-Lactamase-Producing Bacteria

2015 ◽  
Vol 59 (9) ◽  
pp. 5095-5096 ◽  
Author(s):  
Jesús Rodríguez-Baño
Keyword(s):  
Antimicrobial Agents ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Global Spread ◽  
Invasive Infections ◽  
The Times ◽  
Lactamase Inhibitor

ABSTRACTSeveral antimicrobial agents are being investigated as alternatives to carbapenems in the treatment of infections caused by ESBL-producingEnterobacteriaceae, which may be useful in avoiding overuse of carbapenems in the context of recent global spread of carbapenem-resistantEnterobacteriaceae. The most promising candidates for invasive infections so far are β-lactam/β-lactamase inhibitor combinations and cephamycins.

scholarly journals Impact of Delays between Clinical and Laboratory Standards Institute and Food and Drug Administration Revisions of Interpretive Criteria for Carbapenem-Resistant Enterobacteriaceae

2016 ◽  
Vol 54 (11) ◽  
pp. 2757-2762 ◽  
Author(s):  
Sarah M. Bartsch ◽  
Susan S. Huang ◽  
Kim F. Wong ◽  
Rachel B. Slayton ◽  
James A. McKinnell ◽  
...  
Keyword(s):  
Simulation Model ◽  
Drug Administration ◽  
Orange County ◽  
Food And Drug Administration ◽  
Emerging Pathogens ◽  
Policy Makers ◽  
Content Type ◽  
Contact Precautions ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

Delays often occur between CLSI and FDA revisions of antimicrobial interpretive criteria. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model, we found that the 32-month delay in changing carbapenem-resistant Enterobacteriaceae (CRE) breakpoints might have resulted in 1,821 additional carriers in Orange County, CA, an outcome that could have been avoided by identifying CRE and initiating contact precautions. Policy makers should aim to minimize the delay in the adoption of new breakpoints for antimicrobials against emerging pathogens when containment of spread is paramount; delays of <1.5 years are ideal.

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