Carbapenem Resistance In Enterobacteriaceae Research Articles

Environmental contamination by carbapenem-resistant Enterobacteriaceae.

In the last decade, the global emergence of carbapenem resistance in Enterobacteriaceae has posed great concern to public health. Data concerning the role of environmental contamination in the dissemination of carbapenem-resistant Enterobacteriaceae (CRE) are currently lacking. Here, we aimed to examine the extent of CRE contamination in various sites in the immediate surroundings of CRE carriers and to assess the effects of sampling time and cleaning regimens on the recovery rate. We evaluated the performance of two sampling methods, CHROMAgar KPC contact plate and eSwab, for the detection of environmental CRE. eSwab was followed either by direct plating or by broth enrichment. First, 14 sites in the close vicinity of the carrier were evaluated for environmental contamination, and 5, which were found to be contaminated, were further studied. The environmental contamination decreased with distance from the patient; the bed area was the most contaminated site. Additionally, we found that the sampling time and the cleaning regimen were critical factors affecting the prevalence of environmental CRE contamination. We found that the CHROMAgar KPC contact plate method was a more effective technique for detecting environmental CRE than were eSwab-based methods. In summary, our study demonstrated that the vicinity of patients colonized with CRE is often contaminated by these organisms. Using selective contact plates to detect environmental contamination may guide cleaning efficacy and assist with outbreak investigation in an effort to limit the spread of CRE.

Carbapenem-Resistant Enterobacteriaceae: An Emerging Problem in Children

Antibiotic resistance among gram-negative bacteria has reached critical levels. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Carbapenem-resistant Enterobacteriaceae (CRE) infections are known to be associated with significant morbidity and mortality, and these pathogens have now made their way to the most vulnerable populations, including children. This review provides a brief overview of CRE, with a focus on CRE infections in children, and highlights available data on the epidemiology, clinical characteristics, carbapenemase types, risk factors, treatment, and outcomes of these multi-drug resistant infections in the pediatric population.

Primer caso de detección de blaKpc en Chile: desde Italia a un hospital público de Santiago

Carbapenem resistance in Enterobacteriaceae is an emerging problem worldwide. Among the mechanisms involved are the production of ESBLs or AmpC associated with porins loss or the presence of carbapenemases. Among these, the KPC betalactamase has become especially relevant given its rapid spread.In this article we present the first case of isolation of a strain of KPC producer Klebsiella pneumoniae at a hospital in Santiago, in a patient coming from Italy, with a history of multiple hospitalizations for treatment of non-Hodgkin lymphoma and subjected to several cycles of chemotherapy and hemodialysis. The strain was isolated from a urine culture on the seventh day of the patient's arrival to Chile. The isolate was resistant to quinolones, aminoglycosides, cephalosporins and carbapenems, retaining only susceptibility to tigecycline and colistin. In phenotypic test it was found to have positive Hodge test and positive synergy with carbapenems/boronic acid. Polymerase chain reaction demonstrated the presence of beta-lactamases TEM, SHV and KPC-2. None other Class A serine-carbapenemase or metallo-bectalactamases were present.

First Identification of bla IMI-1 in an Enterobacter cloacae Clinical Isolate from France

Carbapenem resistance in Enterobacteriaceae is a growing concern worldwide ([13][1]). Resistance to carbapenems may be mediated by two mechanisms: hyperproduction of an AmpC-type cephalosporinase or extended-spectrum β-lactamase (ESBL) combined with decreased drug permeability through the outer

Molecular diversity in mechanisms of carbapenem resistance in paediatric Enterobacteriaceae

Development of carbapenem resistance in Enterobacteriaceae has impacted Clinical and Laboratory Standards Institute (CLSI) guidelines, infection control approaches and treatment strategies. The clinical, phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae (CRE) infections at paediatric referral centres are not well described. CRE were identified through the clinical microbiology laboratory at Seattle Children's Hospital (Seattle, WA). Clinical data were retrieved from medical records. Resistance testing, polymerase chain reaction (PCR) for resistance determinants, and Escherichia coli transformation were carried out for each isolate. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used to characterise strain relatedness. PCR amplification and sequencing as well as sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) were used to investigate porin alterations. Six CRE isolates were identified between 2002 and 2010. Significant molecular diversity was documented in their mechanisms of resistance, including plasmid-mediated serine carbapenemase (KPC) and metallo-β-lactamase (IMP), chromosomally encoded β-lactamase (SME) and porin alterations with extended-spectrum β-lactamases. Patients had underlying health conditions and were from geographically diverse regions. In one case, PFGE of serial isolates documented the development of resistance in a previously susceptible strain. Molecular investigation of this strain identified insertion of the genetic mobile element insertion sequence IS Ecp1 in the ompK36 gene, conferring a functional porin alteration as demonstrated by SDS-PAGE. This is the first description of porin disruption by IS Ecp1 in a CTX-M-15-positive isolate. This is the largest report of paediatric CRE to date. This diverse description of demographic, phenotypic and molecular characteristics highlights the challenge of CRE infections in high-risk paediatric patients and that attention to emerging resistance mechanisms (including membrane alteration) at paediatric referral centres is essential.

Genotypic characterization and in vitro activities of tigecycline and polymyxin B for members of the Enterobacteriaceae with decreased susceptibility to carbapenems

Carbapenem resistance in members of the Enterobacteriaceae is increasing. To evaluate the effects of tigecycline and polymyxin B against carbapenem-non-susceptible pathogens, 89 representative clinical carbapenem-non-susceptible Enterobacteriaceae isolates were recovered from seven hospitals from four cities in China during 2006-2009: 30 Serratia marcescens, 35 Klebsiella pneumoniae, seven Enterobacter cloacae, six Enterobacter aerogenes, five Escherichia coli, four Citrobacter freundii and two Klebsiella oxytoca isolates. Twenty-eight S. marcescens isolates were indistinguishable. The 35 K. pneumoniae isolates belonged to 12 clonal strains. Among the 89 Enterobacteriaceae isolates, 82 produced KPC-2, seven produced IMP (three produced KPC-2 simultaneously), three did not produce any carbapenemases and nine were deficient in porins. Polymyxin B was much more active than tigecycline against carbapenem-non-susceptible Enterobacteriaceae. The MIC(50) and MIC(90) of imipenem, meropenem, ertapenem, polymyxin B and tigecycline were 8 and 32 µg ml(-1), 8 and 32 µg ml(-1), 16 and 128 µg ml(-1), 0.5 and 16 µg ml(-1), and 4 and 16 µg ml(-1), respectively. Rates of susceptibility to imipenem, meropenem, ertapenem and polymyxin B were 30.0%, 27.5%, 2.5% and 89.2% by CLSI criteria. The rate of susceptibility to tigecycline was 40% and 17.5% by Food and Drug Administration (MIC ≤2 µg ml(-1)) and European Committee on Antimicrobial Susceptibility Testing (MIC ≤1 µg ml(-1)) criteria, respectively. KPC-2- or IMP-producing E. coli transconjugants exhibited reduced susceptibility to carbapenems but were susceptible to polymyxin B and tigecycline with an MIC range of 0.5-2 µg ml(-1), 0.25-2 µg ml(-1), 0.5-4 µg ml(-1), 0.5 µg ml(-1) and 0.5-1 µg ml(-1). In conclusion, carbapenem resistance in Enterobacteriaceae is mainly due to production of KPC-2, and polymyxin B is active for the carbapenem-resistant Enterobacteriaceae.

First detection of oxacillinase-mediated resistance to carbapenems inKlebsiellapneumoniaefrom Morocco

The frequency of carbapenem resistance due to class-D beta-lactamases (i.e. oxacillinases) among the world's Enterobacteriaceae is increasing. Recently, in Morocco, two isolates of carbapenem-resistant Klebsiella pneumoniae were recovered from the same patient, one harbouring plasmid-encoded bla-(OXA-48) and the other the bla-(OXA-1) gene. This represents the first evidence of bla(OXA-48)-mediated carbapenem-resistance in Enterobacteriaceae in Morocco.

Multicenter evaluation of tigecycline activity in Latin America: Report from the SENTRY antimicrobial surveillance program (2009)

Background: Tigecycline, the initial representative of the glycylcyclines, presents a therapy option for emerging multidrug-resistant (MDR) pathogens. India, a nation rarely monitored in global surveillance programs, appears in need of agents active against MDR isolates of Enterobacteriaceae (ESBLs), Acinetobacters (carbapenem-resistant) and Grampositive cocci (MRSA, VRE). Numerous sites were sampled using reference susceptibility methods. Methods: Eleven sites forwarded 1,714 strains to a regional monitor (WCH, Adelaide, Australia) that susceptibility tested 27 antimicrobials by CLSI methods (M7-A7, 2006). Identifications were confirmed and interpretive/screening criteria were also by CLSI guidelines (M100-S18, 2008), except for tigecycline where United States Food and Drug Administration breakpoints were applied. Major pathogens were: S. aureus (250), coagulase-negative staphylococci (CoNS; 228), enterococci (93), Enterobacter spp. (76), E. coli (217), K. pneumoniae (268), Salmonella spp. (55) and Acinetobacter spp. (108). Results: Tigecycline was active against 98-100% of indicated/ tabulated species, lowest for Acinetobacter spp. S. aureus tigecycline MIC90 values were not influenced by oxacillin susceptibility patterns (0.25 mg/L; 100% S). Increased resistance patterns noted were: tetracycline-resistant (4-100%; average 53%), AmpC, ESBLand fluoroquinolone resistance in Enterobacteriaceae (8-70, 14-78, 1-91%, respectively), VRE (1%), MRSA (36%) and Acinetobacters carbapenem-resistant (38%). S. typhi and S. paratyphi were common (tigecycline MIC90, 0.5 mg/L), and 84% were nalidixic acid-resistant. Carbapenem resistance in Enterobacteriaceae (1-7%) was consistent with harbouring metallo-s-lactamases; confirmed by PCR testing. Cum. % inhibited at MIC (mg/L): Organism (no. tested) ≤0.06 0.12 0.25 0.5 1 2 4 % S S. aureus (250) 9 58 98 100 100.0 Enterococci (93) 12 70 100 100.0 E. coli (217) 1 23 76 >99 100 100.0 Enterobacters (76) 0 1 16 79 93 100 100.0 K. pneumoniae (268) 0 0 24 74 96 99 >99 98.5 Salmonella spp. (55) 0 15 56 98 100 100.0 Acinetobacters (108) 2 21 40 75 95 98 >99 98.1 a. US-FDA and Jones et al. (2007) criteria. Conclusions: Although MDR rates across Gram-positive and -negative species (particularly among enteric bacilli and Acinetobacters) was high in India, tigecycline remained active (MIC90, 1 mg/L overall) against these MDR strains. Tigecycline exhibited promising spectrum/potency exceeding currently available agents against sampled isolates from India.

Multicenter Evaluation of Tigecycline Activity in India: Report from the SENTRY Antimicrobial Surveillance Program (2006)

Background: Tigecycline, the initial representative of the glycylcyclines, presents a therapy option for emerging multidrug-resistant (MDR) pathogens. India, a nation rarely monitored in global surveillance programs, appears in need of agents active against MDR isolates of Enterobacteriaceae (ESBLs), Acinetobacters (carbapenem-resistant) and Gram-positive cocci (MRSA, VRE). Numerous sites were sampled using reference susceptibility methods. Methods: Eleven sites forwarded 1,714 strains to a regional monitor (WCH, Adelaide, Australia) that susceptibility tested 27 antimicrobials by CLSI methods (M7-A7, 2006). Identifications were confirmed and interpretive/screening criteria were also by CLSI guidelines (M100-S18, 2008), except for tigecycline where United States - Food and Drug Administration breakpoints were applied. Major pathogens were: S. aureus (250), coagulase-negative staphylococci (CoNS; 228), enterococci (93), Enterobacters (76), E. coli (217), K. pneumoniae (268), Salmonella spp. (55) and Acinetobacters (108). Results: Tigecycline was active against 98–100% of indicated/tabulated species, lowest for Acinetobacter spp. S. aureus tigecycline MIC90 values were not influenced by oxacillin susceptibility patterns (0.25 mg/L; 100% S). Increased resistance patterns noted were: tetracycline-resistant (4–100%; average 53%), AmpC, ESBL- and fluoroquinolone resistance in Enterobacteriaceae (8–70, 14–78, 1–91%, respectively), VRE (1%), MRSA (36%) and Acinetobacters carbapenem-resistant (38%). S. typhi and S. paratyphi were common (tigecycline MIC90, 0.5 mg/L), and 84% were nalidixic acid-resistant. Carbapenem resistance in Enterobacteriaceae (1–7%) was consistent with harbouring metallo-β-lactamases; confirmed by PCR testing. Conclusions: Although MDR rates across Gram-positive and -negative species (particularly among enteric bacilli and Acinetobacters) was high in India, tigecycline remained active (MIC90, 1 mg/L overall) against these MDR strains. Tigecycline exhibited promising spectrum/potency exceeding currently available agents against sampled isolates from India.

Class A carbapenemases

Carbapenems, such as imipenem and meropenem, are most often used to treat infections caused by enterobacteria that produce extended-spectrum beta-lactamases, and the emergence of enzymes capable of inactivating carbapenems would therefore limit the options for treatment. Carbapenem resistance in Enterobacteriaceae is rare, but class A beta-lactamases with activity against the carbapenems are becoming more prevalent within this bacterial family. The class A carbapenemases can phylogenetically be segregated into six different groups of which four groups are formed by members of the GES, KPC, SME, IMI/NMC-A enzymes, while SHV-38 and SFC-1 each separately constitute a group. The genes encoding the class A carbapenemases are either plasmid-borne or located on the chromosome of the host. The bla(GES) genes reside as gene cassettes on mainly class I integrons, whereas the bla(KPC) genes and a single bla(IMI-2) gene are flanked by transposable elements on plasmids. Class A carbapenemases hydrolyse penicillins, classical cephalosporins, monobactam, and imipenem and meropenem, and the enzymes are divided into four phenotypically different groups, namely group 2br, 2be, 2e and 2f, according to the Bush-Jacoby-Medeiros classification system. Class A carbapenemases are inhibited by clavulanate and tazobactam like other class A beta-lactamases.

Ertapenem resistance among Klebsiella and Enterobacter submitted in the UK to a reference laboratory

The emergence of carbapenem resistance in Enterobacteriaceae represents a major public health concern. We investigated ertapenem-resistant clinical isolates of Klebsiella spp. and Enterobacter spp. referred to the UK's national reference laboratory for antibiotic resistance. Minimum inhibitory concentrations (MICs) were determined and interpreted according to British Society for Antimicrobial Chemotherapy guidelines. Genes for carbapenemases and CTX-M extended-spectrum β-lactamases (ESBLs) were sought by polymerase chain reaction, and imipenem hydrolysis was determined by spectrophotometry with crude extracts. From June 2004 to April 2006, 95 Klebsiella spp. and 76 Enterobacter spp. isolates resistant to ertapenem (MICs >2 mg/L) were received, 40% of which (38 Klebsiella spp. and 30 Enterobacter spp.) were highly resistant to ertapenem (MICs >16 mg/L). Imipenem and meropenem were active (geometric mean MICs <2 mg/L) against most isolates with low-level ertapenem resistance but were less active against highly ertapenem-resistant isolates. Only one ertapenem-resistant isolate produced a defined carbapenemase, a Klebsiella pneumoniae with IMP-1 enzyme; one Enterobacter sp. also hydrolysed imipenem, but its carbapenemase remains to be identified. Geometric mean MICs of ertapenem for the collection were reduced five-fold by clavulanic acid for Klebsiella spp. compared with eight-fold by cloxacillin for Enterobacter spp. This study highlights the fact that ertapenem resistance is being detected in Klebsiella spp. and Enterobacter spp. in the UK, but that it is rarely mediated by true carbapenemases. Rather, it probably results from combinations of a β-lactamase – often a CTX-M ESBL in Klebsiella spp. or an AmpC enzyme in Enterobacter spp. – plus impermeability and/or increased efflux. Imipenem and meropenem often remain moderately active against isolates with low-level ertapenem resistance.

First detection of a VIM-1 metallo-β-lactamase in a carbapenem-resistant Citrobacter freundii clinical isolate in an acute hospital in Germany

We report the first detection of a carbapenem-resistant Citrobacter freundii clinical strain in Germany. It was isolated from an abscess of a patient with acute necrotic pancreatitis in an acute hospital. PCR and sequencing experiments revealed that the carbapenem resistance was mediated by a VIM-1 metallo-beta-lactamase, located on a plasmid encoded class 1 integron. Carbapenem resistance in Enterobacteriaceae is so far a rare event and 1 of the major therapeutic concerns in the future.