Distinctive features of ertapenem mono-resistant carbapenem-resistant Enterobacterales in the United States: A cohort study

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem mono-resistant) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed laboratory- and population-based surveillance data from nine sites participating in CDC’s Emerging Infections Program (EIP). We defined an incident case as the first isolation of Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem (determined at clinical laboratory) from a normally sterile site or urine identified from a resident of the EIP catchment area in 2016-2017. We compared risk factors, carbapenemase genes (determined via polymerase chain reaction at CDC), and mortality of cases with ertapenem “mono-resistant” to “other” CRE (resistant to ≥ 1 carbapenem other than ertapenem). We additionally conducted survival analysis to determine the effect of ertapenem mono-resistant status and isolate source (sterile vs. urine) on survival. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE (Figure 1). Ertapenem mono-resistant CRE cases were more frequently ≥ 80 years old (29.1% vs. 19.5%, p< 0.0001), female (67.9% vs 59.0%, p< 0.0001), and white (62.6% vs. 45.1%, p< 0.0001). Ertapenem mono-resistant isolates were more likely than other CRE to be Enterobacter cloacae complex (48.4% vs. 15.4%, p< 0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p< 0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p< 0.0001) (Figure 2). Ertapenem mono-resistance was not associated with difference in 90-day mortality (unadjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.63-1.06) in logistic models or survival analysis (Figure 3). Figure 1. Flow diagram of carbapenem-resistant Enterobacterales cases included in analysis, 2017-2018. CRE, carbapenem-resistant Enterobacterales; MIC, minimum inhibitory concentration. Ertapenem mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. We excluded isolates that (1) had no interpretable MICs for any carbapenem, (2) were only tested against ertapenem, (3) had unknown death status, or (4) were not associated with patient’s first incident case. Figure 2. Proportion of ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) vs. other CRE isolates with specific carbapenemase genes. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-ß-lactamase; OXA, oxacillinase. Ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Testing via reverse transcriptase polymerase chain reaction. Figure 3. Survival analysis comparing patients with carbapenem-resistant Enterobacterales (CRE) that are ertapenem mono-resistant to other CRE (i.e., resistant to ≥1 carbapenem other than ertapenem), either total (A) or stratified by isolate site (B). Ertapenem mono-resistant) isolates were not associated with decreased mortality, and sterile isolate source (i.e., non-urinary isolates) was associated with increased mortality regardless of ertapenem mono-resistance. Conclusion Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics compared to other CRE. These findings may inform antibiotic choice particularly when testing for carbapenemases is not readily available. Disclosures All Authors: No reported disclosures

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Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02578-16 ◽

2017 ◽

Vol 61 (5) ◽

Cited By ~ 15

Author(s):

David A. Boyd ◽

Laura F. Mataseje ◽

Ross Davidson ◽

Johannes A. Delport ◽

Jeff Fuller ◽

...

Keyword(s):

Enterobacter Cloacae ◽

Reference Laboratory ◽

Chromosomal Locus ◽

Complex Species ◽

Content Type ◽

Class A ◽

Carbapenem Resistant ◽

Carbapenemase Gene ◽

Enterobacter Ludwigii ◽

Enterobacter Cloacae Complex

ABSTRACT Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A bla NMC-A or bla IMI-type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, bla NMC-A was highly associated with Enterobacter ludwigii. Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A (n = 10), IMI-1 (n = 5), and IMI-9 (n = 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, bla IMI-5 and bla IMI-6, were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring bla NMC-A/IMI-type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential.

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Characteristics Associated with Death in Patients with Carbapenem-Resistant Acinetobacter baumannii, United States, 2012–2017

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.544 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s59-s60

Author(s):

Hannah E. Reses ◽

Kelly Hatfield ◽

Jesse Jacob ◽

Chris Bower ◽

Elisabeth Vaeth ◽

...

Keyword(s):

Septic Shock ◽

Acinetobacter Baumannii ◽

Treatment Options ◽

Care Facility ◽

Severe Illness ◽

Emerging Infections ◽

Term Care ◽

Icu Stay ◽

Carbapenem Resistant ◽

Sterile Site

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of healthcare-associated infections with limited treatment options and high mortality. To describe risk factors for mortality, we evaluated characteristics associated with 30-day mortality in patients with CRAB identified through the Emerging Infections Program (EIP). Methods: From January 2012 through December 2017, 8 EIP sites (CO, GA, MD, MN, NM, NY, OR, TN) participated in active, laboratory-, and population-based surveillance for CRAB. An incident case was defined as patient’s first isolation in a 30-day period of A. baumannii complex from sterile sites or urine with resistance to ≥1 carbapenem (excluding ertapenem). Medical records were abstracted. Patients were matched to state vital records to assess mortality within 30 days of incident culture collection. We developed 2 multivariable logistic regression models (1 for sterile site cases and 1 for urine cases) to evaluate characteristics associated with 30-day mortality. Results: We identified 744 patients contributing 863 cases, of which 185 of 863 cases (21.4%) died within 30 days of culture, including 113 of 257 cases (44.0%) isolated from a sterile site and 72 of 606 cases (11.9%) isolated from urine. Among 628 hospitalized cases, death occurred in 159 cases (25.3%). Among hospitalized fatal cases, death occurred after hospital discharge in 27 of 57 urine cases (47.4%) and 21 of 102 cases from sterile sites (20.6%). Among sterile site cases, female sex, intensive care unit (ICU) stay after culture, location in a healthcare facility, including a long-term care facility (LTCF), 3 days before culture, and diagnosis of septic shock were associated with increased odds of death in the model (Fig. 1). In urine cases, age 40–54 or ≥75 years, ICU stay after culture, presence of an indwelling device other than a urinary catheter or central line (eg, endotracheal tube), location in a LTCF 3 days before culture, diagnosis of septic shock, and Charlson comorbidity score ≥3 were associated with increased odds of mortality (Fig. 2). Conclusion: Overall 30-day mortality was high among patients with CRAB, including patients with CRAB isolated from urine. A substantial fraction of mortality occurred after discharge, especially among patients with urine cases. Although there were some differences in characteristics associated with mortality in patients with CRAB isolated from sterile sites versus urine, LTCF exposure and severe illness were associated with mortality in both patient groups. CRAB was associated with major mortality in these patients with evidence of healthcare experience and complex illness. More work is needed to determine whether prevention of CRAB infections would improve outcomes.Funding: NoneDisclosures: None

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Abstract 17019: Obesity and Cardiovascular Health in Young American Adults

Circulation ◽

10.1161/circ.142.suppl_3.17019 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Sarabjeet S Suri ◽

Vibhu Parcha ◽

Rajat Kalra ◽

Garima Arora ◽

Pankaj Arora

Keyword(s):

Risk Factors ◽

Young Adults ◽

Cardiovascular Health ◽

Piecewise Linear ◽

The United States ◽

Obesity Prevalence ◽

Logistic Regression Models ◽

Prevalence Of Obesity ◽

Adjusted Logistic Regression ◽

The Impact

Background: The growing epidemic of obesity in the United States (US) is associated with cardiovascular (CV) morbidity and mortality. We evaluated the impact of the increasing obesity prevalence on the CV health of young American adults. Methods: The age-adjusted weighted prevalence of hypertension, diabetes, and hypercholesterolemia was estimated from the 2008-2018 National Health and Nutrition Examination Survey (NHANES) in American adults aged 18-44 years, stratified by the presence of obesity. The trends were evaluated using a piecewise linear regression approach. The odds for CV risk factors were estimated using multivariable-adjusted logistic regression models. Results: Among 14,919 young adults, the prevalence of obesity was 33.9% (95% CI: 32.6-35.3%). Obese young adults were more likely to be non-Hispanic Blacks and in lower socioeconomic and educational attainment strata (p<0.05 for all). Obese young adults had a greater risk of having hypertension (adjusted odds ratio [aOR]: 3.0 [95% CI: 2.7-3.4]), diabetes (aOR: 4.3 [95% CI: 3.3-5.6]), and hyperlipidemia (aOR: 1.47 [95% CI: 1.3-1.7]). Among obese, hypertension increased from 36.5% (33.9-39.1%) in 2007-2010 to 39.4% (35.6-43.1%) in 2015-2018 (p= 0.07) and diabetes increased from 4.7% (3.6-5.8%) in 2007-2010 to 7.1% (5.3-9.0%) in 2015-2018 (p=0.11). A modest increase in diabetes was seen in non-obese individuals ( Table ). Hypercholesterolemia prevalence remained unchanged from 12.6% (95% CI: 10.6-14.7%) 2007-2010 to 10.9% (95% CI: 9.0-12.8%) in 2015-2018 (p=0.27) among obese young adults. Non-obese young adults showed a decline in hypercholesterolemia from 9.5% (95% CI: 8.0-11.0%) in 2007- 2010 to 7.1% (95% CI: 5.8-8.4%) in 2015-2018 (p=0.002). Conclusions: Nearly one-in-every three young American adults have obesity, which is accompanied by a two-fold higher prevalence of CV risk factors. The CV morbidity in young adults is expected to increase with an increasing prevalence of obesity..

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1230. Epidemiology and Risk Factors for Recurrent Invasive Methicillin-Resistant Staphylococcus aureus Infection: nine US States, 2006–2013

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1063 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S373-S374

Author(s):

Ian Kracalik ◽

Kelly Jackson ◽

Joelle Nadle ◽

Wendy Bamberg ◽

Susan Petit ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Infection Type ◽

The United States ◽

Emerging Infections ◽

Methicillin Resistant ◽

Initial Infection ◽

Joint Infections ◽

Mrsa Infection

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) causes >70,000 invasive infections annually in the United States, and recurrent infections pose a major clinical challenge. We examined risk factors for recurrent MRSA infections. Methods We identified patients with an initial invasive MRSA infection (isolation from a normally sterile body site) from 2006 to 2013, through active, population-based surveillance in selected counties in nine states through the Emerging Infections Program. Recurrence was defined as invasive MRSA isolation >30 days after initial isolation. We used logistic regression with backwards selection to evaluate adjusted odds ratios (aOR) associated with recurrence within 180 days, prior healthcare exposures, and initial infection type, controlling for patient demographics and comorbidities. Results Among 24,478 patients with invasive MRSA, 3,976 (16%) experienced a recurrence, including 61% (2,438) within 180 days. Risk factors for recurrence were: injection drug use (IDU) (aOR; 1.38, 95% confidence interval [CI]: 1.15–1.65), central venous catheters (aOR; 1.35, 95% CI: 1.22–1.51), dialysis (aOR; 2.00, 95% CI: 1.74–2.31), and history of MRSA colonization (aOR; 1.35, 95% CI: 1.22–1.51) (figure). Recurrence was more likely for bloodstream infections (BSI) without another infection (aOR; 2.08, 95% CI: 1.74–2.48), endocarditis (aOR; 1.46, 95% CI: 1.16–1.55), and bone/joint infections (aOR; 1.38, 95% CI: 1.20–1.59), and less likely for pneumonia (aOR: 0.75, 95% CI: 0.64–0.89), compared with other initial infection types. When assessed separately, the presence of a secondary BSI with another infection increased the odds of recurrence over that infection without a BSI (aOR: 1.96, 95% CI: 1.68–2.30). Conclusion Approximately one in six persons with invasive MRSA infection had recurrence. We identified potential opportunities to prevent recurrence through infection control (e.g., management and early removal of central catheters). Other possible areas for preventing recurrence include improving the management of patients with BSI and bone/joint infections (including both during and after antibiotic treatment) and mitigating risk of infection from IDU. Disclosures All authors: No reported disclosures.

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Contrasting Crash- and Non-Crash-Involved Riders: Analysis of Data from the Motorcycle Crash Causation Study

Transportation Research Record Journal of the Transportation Research Board ◽

10.1177/0361198119851722 ◽

2019 ◽

Vol 2673 (7) ◽

pp. 122-131 ◽

Cited By ~ 1

Author(s):

Hitesh Chawla ◽

Ilker Karaca ◽

Peter T. Savolainen

Keyword(s):

Risk Factors ◽

Public Health Problem ◽

The United States ◽

Crash Risk ◽

Volume Data ◽

Logistic Regression Models ◽

Significant Public Health Problem ◽

Significant Public Health ◽

Paired Control ◽

Motorcycle Crashes

Motorcycle crashes and fatalities remain a significant public health problem as fatality rates have increased substantially as compared to other vehicle types in the United States. Analysis of causal factors for motorcycle crashes is often challenging given a lack of reliable traffic volume data and the fact that such crashes comprise a relatively small portion of all traffic crashes. Given these limitations, on-scene crash investigations represent an ideal setting through which to investigate the precipitating factors for motorcycle-involved crashes. This study examines motorcycle crash risk factors by employing data recently made available from the Federal Highway Administration Motorcycle Crash Causation Study (MCCS). The MCCS represents a comprehensive investigative effort to determine the causes of motorcycle crashes and involved the collection of in-depth data from 351 crashes, as well as the collection of comparison data from 702 paired control observations in Orange County, California. This dataset provides a unique opportunity to understand how the risk of crash involvement varies across different segments of the riding population. Logistic regression models are estimated to identify the rider and vehicle attributes associated with motorcycle crashes. The results of the study suggest that motorcycle crash risks are related to rider age, physical status, and educational attainment. In addition to such factors outside of the rider’s control, several modifiable risk factors, which arguably affect the riders’ proclivity to take risks, were also found to be significantly associated with motorcycle crash risk, including motorcycle type, helmet coverage, motorcycle ownership, speed, trip destination, and traffic violation history.

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Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

mBio ◽

10.1128/mbio.02994-19 ◽

2019 ◽

Vol 10 (6) ◽

Cited By ~ 3

Author(s):

Natalia Malachowa ◽

Scott D. Kobayashi ◽

Adeline R. Porter ◽

Brett Freedman ◽

Patrick W. Hanley ◽

...

Keyword(s):

United States ◽

Risk Factors ◽

Health Care ◽

Lower Respiratory Tract ◽

The United States ◽

Multidrug Resistant ◽

Sequence Type ◽

Content Type ◽

Carbapenem Resistant ◽

Cynomolgus Macaques

ABSTRACT Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types. IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

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Enterobacter cloacae Complex Sequence Type 171 Isolates Expressing KPC-4 Carbapenemase Recovered from Canine Patients in Ohio

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01161-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 2

Author(s):

Joshua B. Daniels ◽

Liang Chen ◽

Susan V. Grooters ◽

Dixie F. Mollenkopf ◽

Dimitria A. Mathys ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Companion Animals ◽

Enterobacter Cloacae ◽

Sequence Type ◽

Resistant Bacteria ◽

Whole Genome ◽

Content Type ◽

Complex Sequence ◽

Enterobacter Cloacae Complex

ABSTRACT Companion animals are likely relevant in the transmission of antimicrobial-resistant bacteria. Enterobacter xiangfangensis sequence type 171 (ST171), a clone that has been implicated in clusters of infections in humans, was isolated from two dogs with clinical disease in Ohio. The canine isolates contained IncHI2 plasmids encoding blaKPC-4. Whole-genome sequencing was used to put the canine isolates in phylogenetic context with available human ST171 sequences, as well as to characterize their blaKPC-4 plasmids.

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Antibody-Mediated Killing of Carbapenem-Resistant ST258Klebsiella pneumoniaeby Human Neutrophils

mBio ◽

10.1128/mbio.00297-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 18

Author(s):

Scott D. Kobayashi ◽

Adeline R. Porter ◽

Brett Freedman ◽

Ruchi Pandey ◽

Liang Chen ◽

...

Keyword(s):

United States ◽

Human Serum ◽

Bactericidal Activity ◽

Strong Support ◽

The United States ◽

Human Neutrophils ◽

Resistant Bacteria ◽

Serum Bactericidal Activity ◽

Carbapenem Resistant ◽

The World

ABSTRACTCarbapenem-resistantKlebsiella pneumoniaeis a problem worldwide. A carbapenem-resistantK. pneumoniaelineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils. We first demonstrated that an isogenicwzydeletion strain is significantly more susceptible to killing by human heparinized blood, serum, and neutrophils than a wild-type ST258 strain. Consistent with the importance of capsule as an immune evasion molecule, rabbit immune serum and purified IgG specific for ST258 capsule polysaccharide type 2 (CPS2) enhanced killing by human blood and serumin vitro. Moreover, antibodies specific for CPS2 promoted phagocytosis and killing of ST258 by human neutrophils. Collectively, our findings suggest that ST258 CPS2 is a viable target for immunoprophylactics and/or therapeutics.IMPORTANCEInfections caused by carbapenem-resistantK. pneumoniaeare difficult to treat, and mortality is high. New prophylactic approaches and/or therapeutic measures are needed to prevent or treat infections caused by these multidrug-resistant bacteria. A strain of carbapenem-resistantK. pneumoniae, classified by multilocus sequence typing as ST258, is present in many regions of the world and is the most prominent carbapenem-resistantK. pneumoniaelineage in the United States. Here we show that rabbit antibodies specific for capsule polysaccharide of ST258 significantly enhance human serum bactericidal activity and promote phagocytosis and killing of this pathogen by human neutrophils. These studies have provided strong support for the idea that development of an immunotherapy (vaccine) for carbapenem-resistantK. pneumoniaeinfections is feasible and has merit.

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Novel Carbapenemases FLC-1 and IMI-2 Encoded by an Enterobacter cloacae Complex Isolated from Food Products

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02338-18 ◽

2019 ◽

Vol 63 (6) ◽

Cited By ~ 4

Author(s):

Michael S. M. Brouwer ◽

Kamaleddin H. M. E. Tehrani ◽

Michel Rapallini ◽

Yvon Geurts ◽

Arie Kant ◽

...

Keyword(s):

General Population ◽

Enterobacter Cloacae ◽

Hydrolytic Activity ◽

Resistant Bacteria ◽

Human Consumption ◽

The Novel ◽

Antibiotic Resistant ◽

Content Type ◽

Class A ◽

Enterobacter Cloacae Complex

ABSTRACT Food for human consumption is screened widely for the presence of antibiotic-resistant bacteria to assess the potential for transfer of resistant bacteria to the general population. Here, we describe an Enterobacter cloacae complex isolated from imported seafood that encodes two carbapenemases on two distinct plasmids. Both enzymes belong to Ambler class A β-lactamases, the previously described IMI-2 and a novel family designated FLC-1. The hydrolytic activity of the novel enzyme against aminopenicillins, cephalosporins, and carbapenems was determined.

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