Emergence and Rapid Regional Spread of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae

Hunter Holmes McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Division of Infectious Diseases, Richmond, Virginia, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 09/2011; 53(6):532-40. DOI: 10.1093/cid/cir482
Source: PubMed


Background. Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are an emerging antibiotic resistance threat with demonstrated epidemic potential. Methods. We conducted an outbreak investigation of KPC-producing Enterobacteriaceae among patients of acute and long-term acute care hospitals (LTACHs) in 4 adjacent counties in Indiana and Illinois from 1 January 2008 through 31 December 2008 (cases). The study used traditional and molecular epidemiologic methods and an adaptation of social network analysis ("exposure network analysis"). Results. Clinical records for 40 (95%) of 42 patients were available. Patients were mostly older with multiple comorbid conditions. Eleven patients (27.5%) died during the index hospitalization or were discharged to hospice; 23 (57.5%) were discharged to a nursing home, and 4 (10.0%) were discharged to home. One LTACH (LTACH-A) was central to the regional outbreak: 24 (60%) of 40 cases were linked to LTACH-A, and at least 10 patients (25%) acquired KPC there. Of 16 cases not linked to LTACH-A, 12 (75%) were linked to 3 nursing homes. Only 4 patients (10%) definitely acquired KPC during an acute care hospital stay. Molecular typing revealed the 31 available KPC-positive K. pneumoniae isolates to be similar and to cluster with epidemic multilocus sequence type 258; 2 KPC-positive Escherichia coli isolates were unique. Conclusions. We observed extensive transfer of KPC-positive patients throughout the exposure network of 14 acute care hospitals, 2 LTACHs, and 10 nursing homes. Although few cases were identified at most institutions, many facilities were affected. Successful control of KPC-producing Enterobacteriaceae will require a coordinated, regional effort among acute and long-term health care facilities and public health departments.

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Available from: L. Silvia Munoz-Price, Sep 16, 2015
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    • "The study of Sanchez et al. [11] showed that K. pneumoniae antimicrobial drug resistance increased for every antimicrobial class studied except tetracyclines and cross-resistance among imipenem-resistant K. pneumoniae was high for ciprofloxacin but lower for amikacin and tetracycline. Pseudomonas aeruginosa, associated with nosocomial infections, rapidly developed resistance to multiple classes of antibiotics and the import of resistance mechanisms on mobile genetic elements was always a concern [12]. Multi-drug-resistant P. aeruginosa was intermediate or resistant to at least three drug classes: β-lactams, carbapenems, aminoglycosides, and fluoroquinolones and the reported rates varied from 0.6% -32% based on geographic location and the type of surveillance study [13]. "
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    ABSTRACT: Abstract This study aimed to determine the emergence and spread of resistant bacteria in Jeddah Ministry of Health hospitals. Sixteen month follow-up (January 2010 to April 2011) study was carried out and clinical isolates of hospitalized patients were collected, identified and their antimicrobial resistance was determined using two automated systems, Phoenix and Vitek 2. Results revealed that 6195 isolates were identified of which 94% (5846/6195) were Gram negatives. In Escherichia coli, the resistance was 40% (681/1703) to ciprofloxacin, 30% (511/1703) to cefepime, 29% (494/1703) to ceftazidime, 8.5% (145/1703) to tazocin and amikacin, 40% (681/1703) to gentamicin and cefuroxime. In Klebsiella pneumonia, the resistance was 48% (550/1147) to ceftazidime, 49% (565/1147) to cefuroxime, 45.5% (522/1147) to cefepime, 38% (436/1147) to gentamicin, 30% (344/1147) to ciprofloxacin, 19% (218/1147) to tazocin, 7.5% (86/1147) to amikacin and 2.4% (27/1147) to imipenem/meropenem. In Acinetobacter bumannii, 79% (850/1076) were resistant to ciprofloxacin, 68.5% (737/1076) to tazocin, 67% (721/1076) to cefepime, 66% (710/1076) to gentamicin and imipenem/meropenem, 65% (699/1076) to ceftazidime, 68% (735/1076) to amikacin and no resistance to colistin was reported. In Pseudomonas aeruginosa, almost 34% (555/1632) were resistant to ceftazidime, 31% (506/1632) to ciprofloxacin, 29% (473/1632) to cefepime, 26.5% (434/1638) to gentamicin, 19% (310/1632) to imipenem/meropenem, 17% (277/1632) to amikacin, and 15.5% (253/1632) were resistant to tazocin. In Gram positive isolates, MRSA counted only for 4.6% (302/6552) and no vancomycin intermediate Staphylococcus aureus (VISA) were detected. In conclusion, the resistance detected in this study is considered high and antibiotic Stewardship Programs is inevitably required. How to cite this paper: Halwani, M.A., Tashkandy, N.A.J., Aly, M.M., Al Masoudi, S.B. and Dhafar, O.O. (2015) Incidence of Antibiotic Resistance Bacteria in Jeddah’s Ministry of Health Hospitals, Saudi Arabia. Advances in Microbiology, 5, 780-786.
    Full-text · Article · Nov 2015 · Advances in Microbiology
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    • "Similar cases have been observed in other countries as well, indicating that such medical infliction is not only confined to Taiwan per se and may potentially emerge as a global problem [6]. To add to this problem, K. pneumoniae strains which produce extended-spectrum beta-lactamases and are highly resistant to a spectrum of antibiotics are emerging worldwide [6]. These strains, also known as K. pneumoniae carbapenemases (KPC)-encoding strains, are often associated with nearly complete antibiotic resistance whereby failure and mortality rates related to pneumonia caused by this pathogen can reach up to 50% even with antibiotic therapy [7]. "
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    ABSTRACT: Klebsiella pneumoniae plays a major role in causing nosocomial infection in immunocompromised patients. Medical inflictions by the pathogen can range from respiratory and urinary tract infections, septicemia and primarily, pneumonia. As more K. pneumoniae strains are becoming highly resistant to various antibiotics, treatment of this bacterium has been rendered more difficult. This situation, as a consequence, poses a threat to public health. Hence, identification of possible novel drug targets against this opportunistic pathogen need to be undertaken. In the complete genome sequence of K. pneumoniae MGH 78578, approximately one-fourth of the genome encodes for hypothetical proteins (HPs). Due to their low homology and relatedness to other known proteins, HPs may serve as potential, new drug targets. Sequence analysis on the HPs of K. pneumoniae MGH 78578 revealed that a particular HP termed KPN_00953 (YcbK) contains a M15_3 peptidases superfamily conserved domain. Some members of this superfamily are metalloproteases which are involved in cell wall metabolism. BLASTP similarity search on KPN_00953 (YcbK) revealed that majority of the hits were hypothetical proteins although two of the hits suggested that it may be a lipoprotein or related to twin-arginine translocation (Tat) pathway important for transport of proteins to the cell membrane and periplasmic space. As lipoproteins and other components of the cell wall are important pathogenic factors, homology modeling of KPN_00953 was attempted to predict the structure and function of this protein. Three-dimensional model of the protein showed that its secondary structure topology and active site are similar with those found among metalloproteases where two His residues, namely His169 and His209 and an Asp residue, Asp176 in KPN_00953 were found to be Zn-chelating residues. Interestingly, induced expression of the cloned KPN_00953 gene in lipoprotein-deficient E. coli JE5505 resulted in smoother cells with flattened edges. Some cells showed deposits of film-like material under scanning electron microscope. We postulate that KPN_00953 is a Zn metalloprotease and may play a role in bacterial cell wall metabolism. Structural biology studies to understand its structure, function and mechanism of action pose the possibility of utilizing this protein as a new drug target against K. pneumoniae in the future.
    Full-text · Article · Feb 2014 · BMC Structural Biology
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    • "Overall, isolation of CRE from any site—whether this represents clinical infection or not—is associated with poor outcomes. In case series, CRE isolation has been associated with all-cause hospital mortality ranging from 29% to 52% (Hyle et al., 2010; Ku et al., 2012; Marchaim et al., 2011; Souli et al., 2010; Won et al., 2011). "
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    ABSTRACT: The emergence of carbapenem resistance in Enterobacteriaceae is an important threat to global health. Reported outcomes of infections with carbapenem-resistant Enterobacteriaceae (CRE) are poor. Very few options remain for the treatment of these virulent organisms. Antibiotics which are currently in use to treat CRE infections include aminoglycosides, polymyxins, tigecycline, fosfomycin, and temocillin. In addition, the role of combination therapy, including carbapenem containing regimens, remains to be defined. There are several important concerns regarding all of these treatment options such as limited efficacy, increasing reports of resistance, and specific toxicities. Data from retrospective studies favor combination therapy over single-agent therapy for the treatment of CRE bloodstream infections. In summary, new antibiotics are greatly needed, as is additional prospective research.
    Preview · Article · Jan 2013 · Diagnostic microbiology and infectious disease
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