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Burnham JP. The Antimicrobial Resistance-Water-Corporate Interface: Exploring the Connections Between Antimicrobials, Water, and Pollution. Trop Med Infect Dis 2025; 10:105. [PMID: 40278778 PMCID: PMC12031052 DOI: 10.3390/tropicalmed10040105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 04/09/2025] [Accepted: 04/11/2025] [Indexed: 04/26/2025] Open
Abstract
Antibiotic resistance is a public health emergency, with ten million deaths estimated annually by the year 2050. Water systems are an important medium for the development and dissemination of antibiotic resistance from a variety of sources, explored in this perspective review. Hospital wastewater and wastewater systems more broadly are breeding grounds for antibiotic resistance because of the nature of their waste and how it is processed. Corporations from various sectors contribute to antibiotic resistance in many direct and indirect ways. Pharmaceutical factory runoff, agricultural antibiotic use, agricultural use of nitrogen fertilizers, heavy metal pollution, air pollution (atmospheric deposition, burning of oil and/or fossil fuels), plastic/microplastic pollution, and oil/petroleum spills/pollution have all been demonstrated to contribute to antibiotic resistance. Mitigation strategies to reduce these pathways to antibiotic resistance are discussed and future directions hypothesized.
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Affiliation(s)
- Jason P Burnham
- Division of Infectious Diseases, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8051, St. Louis, MO 63110, USA
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Chao CM, Lai CC, Yu WL. Epidemiology of extended-spectrum β-lactamases in Enterobacterales in Taiwan for over two decades. Front Microbiol 2023; 13:1060050. [PMID: 36762100 PMCID: PMC9905819 DOI: 10.3389/fmicb.2022.1060050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 12/22/2022] [Indexed: 01/28/2023] Open
Abstract
The emergence of antimicrobial resistance among microorganisms is a serious public health concern, and extended-spectrum β-lactamases (ESBL)-producing Enterobacterales is one of the major concerns among antibiotic-resistant bacteria. Although the prevalence of ESBL in Enterobacterales has been increasing with time, the prevalence of ESBL could differ according to the species, hospital allocation, sources of infections, nosocomial or community acquisitions, and geographic regions. Therefore, we conducted a comprehensive review of the epidemiology of ESBL-producing Enterobacterales in Taiwan. Overall, the rates of ESBL producers are higher in northern regions than in other parts of Taiwan. In addition, the genotypes of ESBL vary according to different Enterobacterales. SHV-type ESBLs (SHV-5 and SHV-12) were the major types of Enterobacter cloacae complex, but Serratia marcescens, Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae were more likely to possess CTX-M-type ESBLs (CTX-M-3 and CTX-M-14). Moreover, a clonal sequence type of O25b-ST131 has been emerging among urinary or bloodstream E. coli isolates in the community in Taiwan, and this clone was potentially associated with virulence, ESBL (CTX-M-15) production, ciprofloxacin resistance, and mortality. Finally, the evolution of the genetic traits of the ESBL-producing Enterobacterales isolates helps us confirm the interhospital and intrahospital clonal dissemination in several regions of Taiwan. In conclusion, continuous surveillance in the investigation of ESBL production among Enterobacterales is needed to establish its long-term epidemiology.
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Affiliation(s)
- Chien-Ming Chao
- Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan,Department of Dental Laboratory Technology, Min-Hwei College of Health Care Management, Tainan, Taiwan
| | - Chih-Cheng Lai
- Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Wen-Liang Yu
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan,Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan,*Correspondence: Wen-Liang Yu,
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Biofilm Formation and Phenotypic Detection of ESBL, MBL, KPC and AmpC Enzymes and Their Coexistence in Klebsiella spp. Isolated at the National Reference Laboratory, Kathmandu, Nepal. MICROBIOLOGY RESEARCH 2021. [DOI: 10.3390/microbiolres12030049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Klebsiella spp. are associated with several nosocomial and opportunistic infections. Increasing antimicrobial resistance of Klebsiella species is aggravated by a number of intrinsic and extrinsic factors. The main aim of this study is to determine antimicrobial resistance due to production of β-lactamase enzymes, extended spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL) and AmpC and Klebsiella pneumoniae carbapenemase (KPC) and biofilm formation in Klebsiella isolates. A total of 2197 non-duplicate specimens of urine, sputum and pus were obtained from the National Public Health Laboratory (NPHL), Kathmandu, Nepal, between February and August 2019. Klebsiella species were isolated, identified and screened for antimicrobial susceptibility testing with the disk diffusion method. Phenotypic detection of ESBL, MBL, KPC and AmpC production was observed and biofilm production was detected by the microtiter plate method. Out of a total of 2197 clinical specimens, bacterial growth was detected in 8% (175/2197) of the specimens. Of the total isolates, 86.3% (151/175) were Gram-negative bacteria and 37.7% (57/151) were Klebsiella spp. Of the total Klebsiella spp., 56% (32/57) were multi drug resistant (MDR), 16% (9/57) were ESBL, 26% (15/57) were MBL, 4% (2/57) were KPC (class A carbapenemase), 16% (9/57) were AmpC producers and 95% (54/57) were biofilm producers. Gentamicin was the most effective antibiotic, followed by cotrimoxazole, as 68% (39/57) and 47% (27/57) of the Klebsiella isolates were susceptible towards these drugs, respectively. The study results show evidence of β-lactamase production, high prevalence of MDR and biofilm producing Klebsiella species. Integrating the test parameters for phenotypic confirmation of ESBL, MBL, AmpC β lactamase and KPC in routine diagnostic procedures can help in the early detection and management of these resistant strains.
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Khah AN, Hakemi-Vala M, Samavat S, Nasiri MJ. Prevalence, serotyping and drug susceptibility patterns of Escherichia coli isolates from kidney transplanted patients with urinary tract infections. World J Biol Chem 2020; 11:112-118. [PMID: 33274016 PMCID: PMC7672941 DOI: 10.4331/wjbc.v11.i3.112] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 08/24/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) are among the main pathogens in urinary tract infections (UTIs) among kidney transplant patients (KTPs).
AIM To estimate the prevalence of ESBL-producing E. coli in KTPs and to evaluate the most prevalent serotypes and antibacterial susceptibility patterns of isolated bacteria in Tehran, Iran.
METHODS A total of 60 clinical isolates of uropathogenic E. coli were collected from 3 kidney transplant centers from April to May 2019. Antimicrobial susceptibility testing was performed by the disk diffusion method as recommended by the Clinical Laboratory and Standards Institute. The serotyping of E. coli isolates was performed by the slide agglutination method. The presence of blaTEM, blaSHV, and blaCTX-M genes was evaluated by polymerase chain reaction.
RESULTS The frequency of ESBL-producing E. coli in KTPs was found to be 33.4%. All of the 60 E. coli isolates were found to be susceptible to doripenem (100%) and ertapenem (100%). High resistance rates to ampicillin (86%), cefotaxime (80%), and cefazolin (77%) were also documented. The most frequent serotypes were serotype I (50%), serotype II (15%), serotype III (25%), and serotype VI (10%). The gene most frequently found was blaTEM (55%), followed by blaCTX-M (51%) and blaSHV (41%).
CONCLUSION Molecular analysis showed that blaTEM was the most common ESBL-encoding gene. The high resistance to β-lactams antibiotics (i.e., ampicillin, cefotaxime, and cefazolin) found in E. coli from KTPs with UTIs remains a serious clinical challenge. Further efforts to control ESBL-producing E. coli should include the careful use of all antibiotics as well as barrier precautions to reduce spread.
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Affiliation(s)
- Atefeh Najafi Khah
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
| | - Mojdeh Hakemi-Vala
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
| | - Shiva Samavat
- Department of Adult Nephrology, School of Medicine, Shahid Labbafinezhad Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1666694516, Iran
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran
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Spreading of extended-spectrum β-lactamase-producing Escherichia coli ST131 and Klebsiella pneumoniae ST11 in patients with pneumonia: a molecular epidemiological study. Chin Med J (Engl) 2020; 132:1894-1902. [PMID: 31408445 PMCID: PMC6708689 DOI: 10.1097/cm9.0000000000000368] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Supplemental Digital Content is available in the text Background: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the important pathogens causing pneumonia. This study aimed to investigate the clinical characteristics and molecular epidemiology of ESBL-producing E. coli and K. pneumoniae causing pneumonia at a large teaching hospital in China. Methods: We collected patient's clinical data and ESBL-producing E. coli and K. pneumoniae strains causing pneumonia (from December 2015 to June 2016) at a hospital in Wuhan. The susceptibilities, multi-locus sequence typing, homologous analysis, ESBL genes by polymerase chain reaction and sequencing were determined. Results: A total of 59 ESBL-producing strains (31 E. coli and 28 K. pneumoniae) isolated from patients with pneumonia were analyzed. The majority of strains were isolated from patients were with hospital-acquired pneumonia (37/59, 62.7%), followed by community-acquired pneumonia (13/59, 22.0%), and ventilator-related pneumonia (9/59, 15.3%). The E. coli ST131 (9 isolates, 29.0%) and K. pneumoniae ST11 (5 isolates, 17.9%) were the predominant sub-types. The most prevalent ESBL gene was CTX-M-14, followed by SHV-77, CTX-M-3, SHV-11, and CTX-M-27. At least 33 (55.9%) of the ESBL-producing strains carried two or more ESBL genes. The ISEcp1 and IS26 were found upstream of all blaCTX-M (CTX-Ms) and of most blaSHV (SHVs) (57.6%), respectively. Moreover, three ESBL-producing K. pneumoniae ST11 strains which were resistant to carbapenems carried the blaNDM-1 and blaKPC-2, two of which also bearing blaOXA-48 were resistant to all antibiotics (including Tigecycline). Conclusions: Hospital-acquired pneumonia is more likely correlated with ESBL-producing E. coli and K. pneumoniae. ESBL-producing E. coli ST131 and multi-drug resistance ESBL-producing, as well as New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemases-2 (KPC-2) bearing K. pneumoniae ST11 are spreading in patients with pneumonia in hospital.
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Burnham JP, Olsen MA, Stwalley D, Kwon JH, Babcock HM, Kollef MH. Infectious Diseases Consultation Reduces 30-Day and 1-Year All-Cause Mortality for Multidrug-Resistant Organism Infections. Open Forum Infect Dis 2018; 5:ofy026. [PMID: 29577058 PMCID: PMC5852998 DOI: 10.1093/ofid/ofy026] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 01/22/2018] [Indexed: 12/16/2022] Open
Abstract
Background Multidrug-resistant organism (MDRO) infections are associated with high mortality and readmission rates. Infectious diseases (ID) consultation improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream infections. Our goal was to determine the association between ID consultation and mortality following various MDRO infections. Methods This study was conducted with a retrospective cohort (January 1, 2006–October 1, 2015) at an academic tertiary referral center. We identified patients with MDROs in a sterile site or bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within 1 year of index culture were identified, and the association of ID consultation with these outcomes was determined using Cox proportional hazards models with inverse weighting by the propensity score for ID consultation. Results A total of 4214 patients with MDRO infections were identified. ID consultation was significantly associated with reductions in 30-day and 1-year mortality for resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.63; and HR, 0.73, 95% CI, 0.61–0.86) and Enterobacteriaceae (HR, 0.41; 95% CI, 0.27–0.64; and HR, 0.74; 95% CI, 0.59–0.94), and 30-day mortality for polymicrobial infections (HR, 0.51; 95% CI, 0.31–0.86) but not Acinetobacter or Pseudomonas. For resistant Enterococcus, ID consultation was marginally associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62–1.06). ID consultation was associated with reduced 30-day readmission for resistant Enterobacteriaceae. Conclusions ID consultation was associated with significant reductions in 30-day and 1-year mortality for resistant S. aureus and Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was no association between ID consultation and mortality for patients with resistant Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes. Our results suggest that ID consultation may be beneficial for patients with some MDRO infections.
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Affiliation(s)
- Jason P Burnham
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Margaret A Olsen
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Dustin Stwalley
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Jennie H Kwon
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Hilary M Babcock
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Marin H Kollef
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
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Makhtar C, Mamadou TM, Awa BD, Assane D, Halimatou DN, Farba K, Seynabou LL, Habsa DS, Safietou NC, Coumba TK, Aïssatou GD, Souleymane M, Cheikh SBB. Extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae clinical isolates in a Senegalese teaching hospital: A cross sectional study. ACTA ACUST UNITED AC 2017. [DOI: 10.5897/ajmr2017.8716] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Tsai MH, Lee IT, Chu SM, Lien R, Huang HR, Chiang MC, Fu RH, Hsu JF, Huang YC. Clinical and Molecular Characteristics of Neonatal Extended-Spectrum β-Lactamase-Producing Gram-Negative Bacteremia: A 12-Year Case-Control-Control Study of a Referral Center in Taiwan. PLoS One 2016; 11:e0159744. [PMID: 27505270 PMCID: PMC4978492 DOI: 10.1371/journal.pone.0159744] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Accepted: 07/07/2016] [Indexed: 11/18/2022] Open
Abstract
Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteremia (GNB) in the neonatal intensive care unit was characterized by comparison with two control groups: a susceptible control group and a general base population group over 2001 to 2012. The influence of ESBL production on mortality was studied in all study subjects and ESBL-GNB isolates were microbiologically characterized. We identified 77 episodes of ESBL-GNB (14.2% of all neonatal late-onset GNB), which were caused by Klebsiella spp. (62.3%), E. coli (20.8%) and Enterobacter spp. (16.9%). Most ESBL-GNB strains were genetically unrelated and the SHV-type ESBLs were the most prevalent (67% of isolates). Comparison with both control groups disclosed previous usage of 3rd generation cephalosporin (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.03–10.97; P < 0.001), and underlying renal disease (OR, 4.07; 95% CI, 1.10–15.08; P = 0.035) as independent risk factors for ESBL-GNB. Inadequate empiric antibiotics, a higher illness severity, higher rates of infectious complications and sepsis-attributable mortality were more frequently seen in neonates with ESBL-GNB than those with non-ESBL GNB (20.8% and 15.6% vs. 9.2% and 7.9%, respectively; P = 0.008 and 0.049, respectively). Neonates with underlying secondary hypertension (OR, 7.22; 95% CI, 2.17–24.06) and infectious complications after bacteremia (OR, 6.66; 95% CI, 1.81–19.31) were identified as independent risk factor for in-hospital mortality. ESBL-GNB accounted for one-seventh of all neonatal gram-negative bacteremia, especially in neonates exposed to broad-spectrum cephalosporins. Neonates with ESBL-GNB bacteremia more frequently received inadequate empirical antibiotic therapy, which were associated with a higher rate of infectious complications and an adverse outcome.
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Affiliation(s)
- Ming-Horng Tsai
- Division of Neonatology and Pediatric Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Yunlin, Taiwan
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung University of Science and Technology, Chiayi, Taiwan
| | - I-Ta Lee
- Department of Anatomy, College of Medicine, China Medical University, Taichung, Taiwan
| | - Shih-Ming Chu
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Reyin Lien
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsuan-Rong Huang
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Chou Chiang
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ren-Huei Fu
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jen-Fu Hsu
- Division of Pediatric Neonatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- * E-mail: (YCH); (JFH)
| | - Yhu-Chering Huang
- Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Pediatric Infectious Disease; Chang Gung Memorial Hospital, Taoyuan, Taiwan
- * E-mail: (YCH); (JFH)
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Nishizaki N, Nakagawa M, Hara S, Oda H, Kantake M, Obinata K, Uehara Y, Hiramatsu K, Shimizu T. Effect of PMX-DHP for sepsis due to ESBL-producing E. coli in an extremely low-birthweight infant. Pediatr Int 2016; 58:411-414. [PMID: 26710929 DOI: 10.1111/ped.12825] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 08/03/2015] [Accepted: 09/03/2015] [Indexed: 12/01/2022]
Abstract
We report a case of early onset sepsis caused by (CTX for cefotaximase and M for Munich)-type extended-spectrum β-lactamase-producing Escherichia coli (ESBL E. coli) in a preterm infant weighing 601 g. He was given meropenem and treated for endotoxin absorption with polymyxin B-immobilized fibers with only 8 mL of priming volume. The patient survived without any short-term neurological or respiratory sequelae. The choice of antibiotics is particularly important in seriously ill neonates with sepsis due to ESBL-producing organisms. Polymyxin B hemoperfusion might be an innovative therapy for severe neonatal sepsis and could improve outcome even in an extremely low-birthweight infant.
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Affiliation(s)
- Naoto Nishizaki
- Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Mayu Nakagawa
- Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Satoshi Hara
- Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Hisayuki Oda
- Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Masato Kantake
- Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Kaoru Obinata
- Department of Pediatrics, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Yuki Uehara
- Department of Bacteriology, Juntendo University School of Medicine, Tokyo, Japan
| | - Keiichi Hiramatsu
- Department of Bacteriology, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan
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Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms. Antimicrob Agents Chemother 2016; 60:2150-6. [PMID: 26810655 DOI: 10.1128/aac.02592-15] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 01/16/2016] [Indexed: 11/20/2022] Open
Abstract
The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints forEnterobacteriaceaein 2014, and MICs of 4 and 8 μg/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 μg/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, ≥30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 μg/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 μg/ml. Prolonged i.v. infusions may be useful for this population.
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Liu HC, Hung YP, Lin HJ, Liu HC, Lee JC, Wu YH, Li CW, Li MC, Ko WC. Antimicrobial susceptibility of clinical Enterobacteriaceae isolates at the emergency department in a regional hospital: A threat of extended spectrum beta-lactamase-producers among nursing home residents. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2015; 49:584-90. [PMID: 26692184 DOI: 10.1016/j.jmii.2015.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Revised: 05/31/2015] [Accepted: 10/08/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND/PURPOSE The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in nursing home residents has rarely been reported in Taiwan. METHODS A retrospective study was performed at medical wards of a district hospital at southern Taiwan between July 2009 and June 2011. Patients were included if they were older than 18 years, admitted via the emergency department, and their blood, sputum, or urine culture revealed the growth of Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. From each patient only the first isolate from the infection site was included. Antimicrobial susceptibility was determined using the disc diffusion method. RESULTS Overall, 827 patients were included, with 354 (42.8%) coming from the community and 473 (57.2%) referred from a nursing home. Of the isolates acquired in nursing home, 45.5% (215/473) harbored ESBL. By contrast, 20.6% (73) of 354 isolates acquired in the community exhibited the ESBL production phenotype (p < 0.001). Of the isolates obtained from blood, urine, or sputum, 28.2% (37/131), 36.0% (208/578), or 36.4% (43/118) harbored ESBL, respectively, whereas 41% (211) of 515 E. coli isolates, 34.3% (72) of 210 K. pneumoniae, and 4.9% (5) of 102 P. mirabilis had ESBL. In general, the isolates from a nursing home or those with ESBL had lower antimicrobial susceptibility rates than those from the community or those without ESBL production. Only amikacin, piperacillin/tazobactam, ertapenem, and imipenem/meropenem were active against >90% Enterobacteriaceae isolates, irrespective of ESBL production. CONCLUSION ESBL production was common among clinical Enterobacteriaceae isolates, especially E. coli or those isolated from nursing home residents.
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Affiliation(s)
- Hsiu-Chuan Liu
- Department of Experiment and Diagnosis and Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan
| | - Yuan-Pin Hung
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital and Medical Colleague, Tainan, Taiwan; Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan, Taiwan
| | - Hsiao-Ju Lin
- Department of Experiment and Diagnosis and Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital and Medical Colleague, Tainan, Taiwan; Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan, Taiwan
| | - Hsiao-Chieh Liu
- Department of Experiment and Diagnosis and Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan
| | - Jen-Chieh Lee
- Department of Internal Medicine, National Cheng Kung University Hospital and Medical Colleague, Tainan, Taiwan
| | - Yi-Hui Wu
- Department of Internal Medicine, E-da Hospital, Kaohsiung, Taiwan
| | - Chia-Wen Li
- Department of Internal Medicine, National Cheng Kung University Hospital and Medical Colleague, Tainan, Taiwan
| | - Ming-Chi Li
- Department of Internal Medicine, National Cheng Kung University Hospital and Medical Colleague, Tainan, Taiwan
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital and Medical Colleague, Tainan, Taiwan.
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Hendrik TC, Voor in ‘t holt AF, Vos MC. Clinical and Molecular Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Klebsiella spp.: A Systematic Review and Meta-Analyses. PLoS One 2015; 10:e0140754. [PMID: 26485570 PMCID: PMC4617432 DOI: 10.1371/journal.pone.0140754] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 09/30/2015] [Indexed: 12/30/2022] Open
Abstract
Healthcare-related infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. are of major concern. To control transmission, deep understanding of the transmission mechanisms is needed. This systematic review aimed to identify risk factors and sources, clonal relatedness using molecular techniques, and the most effective control strategies for ESBL-producing Klebsiella spp. A systematic search of PubMed, Embase, and Outbreak Database was performed. We identified 2771 articles from November 25th, 1960 until April 7th, 2014 of which 148 were included in the systematic review and 23 in a random-effects meta-analysis study. The random-effects meta-analyses showed that underlying disease or condition (odds ratio [OR] = 6.25; 95% confidence interval [CI] = 2.85 to 13.66) generated the highest pooled estimate. ESBL-producing Klebsiella spp. were spread through person-to-person contact and via sources in the environment; we identified both monoclonal and polyclonal presence. Multi-faceted interventions are needed to prevent transmission of ESBL-producing Klebsiella spp.
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Affiliation(s)
- Tirza C. Hendrik
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Anne F. Voor in ‘t holt
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Margreet C. Vos
- Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands
- * E-mail:
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Sidjabat HE, Paterson DL. Multidrug-resistantEscherichia coliin Asia: epidemiology and management. Expert Rev Anti Infect Ther 2015; 13:575-91. [DOI: 10.1586/14787210.2015.1028365] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Vlieghe ER, Huang TD, Phe T, Bogaerts P, Berhin C, De Smet B, Peetermans WE, Jacobs JA, Glupczynski Y. Prevalence and distribution of beta-lactamase coding genes in third-generation cephalosporin-resistant Enterobacteriaceae from bloodstream infections in Cambodia. Eur J Clin Microbiol Infect Dis 2015; 34:1223-9. [PMID: 25717021 PMCID: PMC4426130 DOI: 10.1007/s10096-015-2350-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Accepted: 02/03/2015] [Indexed: 11/30/2022]
Abstract
Resistance to third-generation cephalosporins in Gram-negative bacteria is emerging in Asia. We report the prevalence and distribution of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase-coding genes in cefotaxime-resistant Enterobacteriaceae isolates from bloodstream infections (BSI) in Cambodia. All Enterobacteriaceae isolated from BSI in adult patients at Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia (2007–2010) were assessed. Antimicrobial susceptibility testing was carried out by disc diffusion and MicroScan according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Screening for ESBL, plasmidic AmpC and carbapenemase-coding genes was performed by multiplex polymerase chain reaction (PCR) sequencing assays. Identification of the ST131 clone was performed in all CTX-M-positive Escherichia coli, using PCR targeting the papB gene. Out of 183 Enterobacteriaceae, 91 (49.7 %) isolates (84 BSI episodes) were cefotaxime-resistant: E. coli (n = 68), Klebsiella pneumoniae (n = 17) and Enterobacter spp. (n = 6). Most episodes were community-acquired (66/84; 78.3 %). ESBLs were present in 89/91 (97.8 %) cefotaxime-resistant isolates: 86 (96.6 %) were CTX-M, mainly CTX-M-15 (n = 41) and CTX-M-14 (n = 21). CTX-M of group 1 were frequently associated with TEM and/or OXA-1/30 coding genes and with phenotypic combined resistance to ciprofloxacin, sulphamethoxazole–trimethoprim and gentamicin (39/50, 78.0 %). Plasmidic AmpC (CMY-2 and DHA-1 types) were found alone (n = 2) or in combination with ESBL (n = 4). Eighteen E. coli isolates were identified as B2-ST131-O25B: 11 (61.1 %) carried CTX-M-14. No carbapenemase-coding genes were detected. ESBL among Enterobacteriaceae from BSI in Cambodia is common, mainly associated with CTX-M-15 and CTX-M-14. These findings warrant urgent action for the containment of antibiotic resistance in Cambodia.
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Affiliation(s)
- E R Vlieghe
- Department of Clinical Sciences, Institute of Tropical Medicine, Nationalestraat 155, 2000, Antwerp, Belgium,
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Trends in human fecal carriage of extended-spectrum β-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 2014; 26:744-58. [PMID: 24092853 DOI: 10.1128/cmr.00023-13] [Citation(s) in RCA: 494] [Impact Index Per Article: 44.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
In the last 10 years, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have become one of the main challenges for antibiotic treatment of enterobacterial infections, largely because of the current CTX-M enzyme pandemic. However, most studies have focused on hospitalized patients, though today it appears that the community is strongly affected as well. We therefore decided to devote our investigation to trends in ESBL-E fecal carriage rates and comprehensively reviewed data from studies conducted on healthy populations in various parts of the world. We show that (i) community ESBL-E fecal carriage, which was unknown before the turn of the millennium, has since increased significantly everywhere, with developing countries being the most affected; (ii) intercontinental travel may have emphasized and globalized the issue; and (iii) CTX-M enzymes, especially CTX-M-15, are the dominant type of ESBL. Altogether, these results suggest that CTX-M carriage is evolving toward a global pandemic but is still insufficiently described. Only a better knowledge of its dynamics and biology will lead to further development of appropriate control measures.
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Feng X, Yang X, Yi C, Guo Q, Mao H, Jiang Z, Li Z, Chen D, Cui Y, Yu X. Escherichia coli Peritonitis in peritoneal dialysis: the prevalence, antibiotic resistance and clinical outcomes in a South China dialysis center. Perit Dial Int 2014; 34:308-16. [PMID: 24497589 DOI: 10.3747/pdi.2013.00012] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Escherichia coli (E. coli) peritonitis is a frequent, serious complication of peritoneal dialysis (PD). The extended-spectrum β-lactamase (ESBL)-producing E. coli peritonitis is associated with poorer prognosis and its incidence has been on continuous increase during the last decades. However, the clinical course and outcomes of E. coli peritonitis remain largely unclear. METHODS All of the E. coli peritonitis episodes that occurred in our dialysis unit from 2006 to 2011 were reviewed. The polymicrobial episodes were excluded. RESULTS In total, ninety episodes of monomicrobial E. coli peritonitis occurred in 68 individuals, corresponding to a rate of 0.027 episodes per patient-year. E. coli was the leading cause (59.2%) of monomicrobial gram-negative peritonitis. ESBL-producing strains accounted for 35.5% of E. coli peritonitis. The complete cure rate and treatment failure rate of E. coli peritonitis were 77.8% and 10.0% respectively. Patients with preceding peritonitis had a higher risk of ESBL production as compared to those without peritonitis history [odds ratio (OR): 5.286; 95% confidence interval (CI): 2.018 - 13.843; p = 0.001]. The risk of treatment failure was significantly increased when the patient had a baseline score of Charlson Comorbidity Index (CCI) above 3 (OR: 6.155; 95% CI: 1.198 - 31.612; p = 0.03), or had diabetes mellitus (OR: 8.457; 95% CI: 1.838 - 38.91; p = 0.006), or hypoalbuminemia (≤ 30g/l) on admission (OR: 13.714; 95% CI: 1.602 - 117.428; p = 0.01). Prolonging the treatment course from 2 to 3 weeks or more reduced the risk of relapse and repeat significantly (p < 0.05). CONCLUSIONS E. coli peritonitis remains a common complication of PD. The clinical outcomes of E. coli peritonitis are relatively favorable despite the high ESBL rate. A history of peritonitis is associated with increased risk for ESBL development. The severity of baseline comorbidities, the presence of diabetes mellitus and hypoalbuminemia at admission are associated with poor outcomes.
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Affiliation(s)
- Xiaoran Feng
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiao Yang
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chunyan Yi
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qunying Guo
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Haiping Mao
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zongpei Jiang
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhibin Li
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dongmei Chen
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yingpeng Cui
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xueqing Yu
- Department of Nephrology, Epidemiology and Clinical Research Unit, and Department of Clinical Microbiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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Tsai MH, Chu SM, Hsu JF, Lien R, Huang HR, Chiang MC, Fu RH, Lee CW, Huang YC. Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU. Pediatrics 2014; 133:e322-9. [PMID: 24420803 DOI: 10.1542/peds.2013-1248] [Citation(s) in RCA: 159] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To assess the risk factors antibiotic therapy and outcomes of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bacteremia in NICU patients. METHODS Episodes of MDR GNB bacteremia were compared with a non-MDR GNB bacteremia group in an 8-year cohort study. RESULTS Of 1106 bacteremias, 393 (35.5%) were caused by GNB. Seventy (18.6%) were caused by an MDR strain. The most frequent mechanism of resistance was extended-spectrum β-lactamase production (67.1%), mainly by Klebsiella pneumoniae (59.6%). Previous antibiotic exposure to third-generation cephalosporin (odds ratio [OR]: 5.97; 95% confidence interval [CI]: 2.37-15.08; P < .001) and carbapenem (OR: 3.60; 95% CI: 1.26-10.29; P = .017) and underlying renal disease (OR: 7.08; 95% CI: 1.74-28.83; P = .006) were identified as independent risk factors for MDR GNB acquisition. Patients with MDR GNB bacteremia more likely received inadequate initial antibiotic therapy (72.9% vs 7.8%; P < .001) had higher rates of infectious complication (21.4% vs 10.5%; P = .011) and overall case fatality +rate (28.6% vs 10.5%; P < .001). Independent risk factors for overall mortality were presence of infectious complications after bacteremia (OR: 3.16; 95% CI: 1.41-7.08; P = .005) and underlying secondary pulmonary hypertension with or without cor pulmonale (OR: 6.19; 95% CI: 1.88-20.31; P = .003). CONCLUSIONS MDR GNB accounted for 18.6% of all neonatal GNB bacteremia in the NICU, especially in those with previous broad-spectrum antibiotic therapy and underlying renal disease. The most frequent mechanism of resistance was extended-spectrum β-lactamase (ESBL) production. Neonates with MDR GNB were more likely to develop infectious complications, which were independently associated with a higher overall case-fatality rate.
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Affiliation(s)
- Ming-Horng Tsai
- Division of Neonatology and Pediatric Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Yunlin, Taiwan
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The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. mBio 2013; 4:e00377-13. [PMID: 24345742 PMCID: PMC3870262 DOI: 10.1128/mbio.00377-13] [Citation(s) in RCA: 341] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The Escherichia coli sequence type 131 (ST131) clone is notorious for extraintestinal infections, fluoroquinolone resistance, and extended-spectrum beta-lactamase (ESBL) production, attributable to a CTX-M-15-encoding mobile element. Here, we applied pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing to reconstruct the evolutionary history of the ST131 clone. PFGE-based cluster analyses suggested that both fluoroquinolone resistance and ESBL production had been acquired by multiple ST131 sublineages through independent genetic events. In contrast, the more robust whole-genome-sequence-based phylogenomic analysis revealed that fluoroquinolone resistance was confined almost entirely to a single, rapidly expanding ST131 subclone, designated H30-R. Strikingly, 91% of the CTX-M-15-producing isolates also belonged to a single, well-defined clade nested within H30-R, which was named H30-Rx due to its more extensive resistance. Despite its tight clonal relationship with H30Rx, the CTX-M-15 mobile element was inserted variably in plasmid and chromosomal locations within the H30-Rx genome. Screening of a large collection of recent clinical E. coli isolates both confirmed the global clonal expansion of H30-Rx and revealed its disproportionate association with sepsis (relative risk, 7.5; P < 0.001). Together, these results suggest that the high prevalence of CTX-M-15 production among ST131 isolates is due primarily to the expansion of a single, highly virulent subclone, H30-Rx. We applied an advanced genomic approach to study the recent evolutionary history of one of the most important Escherichia coli strains in circulation today. This strain, called sequence type 131 (ST131), causes multidrug-resistant bladder, kidney, and bloodstream infections around the world. The rising prevalence of antibiotic resistance in E. coli is making these infections more difficult to treat and is leading to increased mortality. Past studies suggested that many different ST131 strains gained resistance to extended-spectrum cephalosporins independently. In contrast, our research indicates that most extended-spectrum-cephalosporin-resistant ST131 strains belong to a single highly pathogenic subclone, called H30-Rx. The clonal nature of H30-Rx may provide opportunities for vaccine or transmission prevention-based control strategies, which could gain importance as H30-Rx and other extraintestinal pathogenic E. coli subclones become resistant to our best antibiotics.
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Saleem AF, Qamar FN, Shahzad H, Qadir M, Zaidi AKM. Trends in antibiotic susceptibility and incidence of late-onset Klebsiella pneumoniae neonatal sepsis over a six-year period in a neonatal intensive care unit in Karachi, Pakistan. Int J Infect Dis 2013; 17:e961-5. [PMID: 23759260 DOI: 10.1016/j.ijid.2013.04.007] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 04/02/2013] [Accepted: 04/05/2013] [Indexed: 12/18/2022] Open
Abstract
INTRODUCTION The incidence, change in antibiotic susceptibility, and risk factors associated with mortality of late-onset Klebsiella pneumoniae sepsis during 2006-2011, in a neonatal intensive care unit (NICU) of a developing country, were analyzed. METHODS The medical records of neonates with a discharge diagnosis of sepsis due to late-onset K. pneumoniae were retrieved. Demographic features, gestational age, date and year of admission, antibiotic susceptibility of isolates, and discharge status were recorded. The late-onset K. pneumoniae incidence per 1000 NICU admissions and risk factors for mortality due to late-onset K. pneumoniae sepsis are reported. RESULTS During the period 2006-2011, 104 of 2768 neonates developed late-onset K. pneumoniae sepsis. The overall incidence of late-onset K. pneumoniae sepsis was 3.7% (37/1000 NICU admissions), with the highest annual incidence being 53/1000 in 2010. Most cases were males (n = 64; 62%) and most were premature and very low birth weight (n = 68; 65%). More than 80% of isolates were resistant to ampicillin + clavulanic acid, gentamicin, aztreonam, and cephalosporins. An increasing trend of resistance to amikacin, fluoroquinolones, piperacillin/tazobactam, and imipenem was observed. In 2011, three-quarters (72%; n=13) of late-onset K. pneumoniae were CR K. pneumoniae. Seventeen (16%) neonates died. Being male (p = 0.06, adjusted odds ratio (AOR) 9.2, 95% confidence interval (CI) 1.3-66.9), having an extremely low birth weight (p = 0.01, AOR 6.1, 95% CI 0.8-44.4), having severe thrombocytopenia (p = 0.07, AOR 3.9, 95% CI 1.2-13.0), and failure to achieve microbiological clearance (p < 0.001, AOR 19.6, 95% CI 4.0-98.0) were significantly associated with mortality due to late-onset K. pneumoniae sepsis. CONCLUSION There has been a rise in carbapenem-resistant strains of late-onset K. pneumoniae, associated with an increased mortality and limited antibacterial choices. Antimicrobial stewardship and rigorous infection control measures seem to be the only way to limit the spread of these strains.
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Affiliation(s)
- Ali Faisal Saleem
- Department of Paediatrics and Child Health, Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi 74800, Pakistan.
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An S, Chen J, Wang Z, Wang X, Yan X, Li J, Chen Y, Wang Q, Xu X, Li J, Yang J, Wang H, Gao Z. Predominant characteristics of CTX-M-producing Klebsiella pneumoniae isolates from patients with lower respiratory tract infection in multiple medical centers in China. FEMS Microbiol Lett 2012; 332:137-45. [PMID: 22537112 DOI: 10.1111/j.1574-6968.2012.02586.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2012] [Revised: 04/23/2012] [Accepted: 04/23/2012] [Indexed: 11/26/2022] Open
Affiliation(s)
- Shuchang An
- Department of Respiratory and Critical Care Medicine; Peking University People's Hospital; Beijing; China
| | - Jichao Chen
- Department of Respiratory Medicine; the Central Hospital of China Aerospace Corporation; Beijing; China
| | - Zhanwei Wang
- Department of Clinical Laboratory; Peking University People's Hospital; Beijing; China
| | - Xiaorong Wang
- Department of Respiratory and Critical Care Medicine; Peking University People's Hospital; Beijing; China
| | - Xixin Yan
- Department of Respiratory Medicine; the Second Hospital of Hebei Medical University; Shijiazhuang; China
| | - Jihong Li
- Department of Clinical Laboratory; the Second Hospital of Hebei Medical University; Shijiazhuang; China
| | - Yusheng Chen
- Department of Respiratory Medicine; Fujian Province Hospital; Fuzhou; China
| | - Qi Wang
- Department of Respiratory Medicine; the Second Affiliated Hospital of Dalian Medical University; Dalian; China
| | - Xiaoling Xu
- Department of Respiratory Medicine; Anhui Province Hospital; Hefei; China
| | - Jiabin Li
- Department of Infectious Diseases; the First Affiliated Hospital of Anhui Medical University; Hefei; China
| | - Jingping Yang
- Department of Respiratory Medicine; the Third Affiliated Hospital of the Inner Mongolia Medical College; Baotou; China
| | - Hui Wang
- Department of Clinical Laboratory; Peking University People's Hospital; Beijing; China
| | - Zhancheng Gao
- Department of Respiratory and Critical Care Medicine; Peking University People's Hospital; Beijing; China
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Nicolas-Chanoine MH. Les entérobactéries productrices de bêta-lactamases à spectre élargi : où sont les dangers ? MEDECINE INTENSIVE REANIMATION 2012. [DOI: 10.1007/s13546-012-0463-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Tawfik AF, Alswailem AM, Shibl AM, Al-Agamy MHM. Prevalence and genetic characteristics of TEM, SHV, and CTX-M in clinical Klebsiella pneumoniae isolates from Saudi Arabia. Microb Drug Resist 2011; 17:383-8. [PMID: 21612509 DOI: 10.1089/mdr.2011.0011] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The prevalence and genetic basis of extended-spectrum beta-lactamases (ESBLs) in Klebsiella pneumoniae remains unclear in Saudi Arabia. Therefore, this study was devoted to determine the prevalence and characterize ESBL-producing K. pneumoniae in Al-Qassim area, Saudi Arabia. A total of 430 isolates of K. pneumoniae isolated from clinical samples were collected over 6 months from January to June 2008. These isolates were screened for the presence of ESBLs by double-disk synergy test and re-evaluated by E-test ESBL method. Minimum inhibitory concentrations of 15 antibiotics against ESBL-positive strains were determined by E-test strips. The β-lactamases involved were characterized by polymerase chain reaction assays and DNA sequencing. Conjugation experiments were done and ISEcp1 elements were tested among CTX-M positive isolates. The prevalence of ESBL was 25.6% (110/430) and all ESBL-positive isolates were sensitive to imipenem and tigecycline; however, the resistance rate to gentamicin, amikacin, and ciprofloxacin was 87.3%, 10%, and 9.1%, respectively. Of these, 89.1% produced SHV, 70.9% produced TEM, and 36.4% were CTX-M-producing strains. The prevalence of ESBL SHV SHV-12 and SHV-5 was of 60% and 18.2%, respectively, and various non-ESBL SHV, including SHV-1 (5.5%), -11 (3.6%), and -85 (1.8%), was detected. However, the prevalence of CTX-M-15 and CTX-M-14 was 34.5% and 1.8%, respectively. ISEcp1 element was detected in 60% of bla(CTX-M-15) genes. All bla(CTX-M) genes were transferable; however, most of bla(SHV-12) and bla(SHV-5) were not transferable. TEM-type ESBLs were not detected in any of the isolates. This is the first description of CTX-M-14, SHV-5, SHV-11, and SHV-85 in Saudi Arabia. We have documented the dominance of K. pneumoniae SHV-12 and highlighted the emergence of CTX-M-15 in Saudi Arabia.
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Affiliation(s)
- Abdulkader F Tawfik
- Department of Pharmaceutics and Microbiology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Comparison of CTX-M-14- and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae isolates from patients with bacteremia. J Infect 2011; 63:39-47. [PMID: 21712135 DOI: 10.1016/j.jinf.2011.05.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Revised: 05/04/2011] [Accepted: 05/04/2011] [Indexed: 11/20/2022]
Abstract
OBJECTIVE Recently, CTX-M-15-producing Enterobacteriaceae has disseminated worldwide. To better understand the success of CTX-M-15-type extended-spectrum β-lactamase, we compared the CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae isolates with CTX-M-14-producing E. coli and K. pneumoniae isolates that had been more prevalent before the recent increase of CTX-M-15 in Korea. METHODS Eighty-nine CTX-M-producing E. coli bloodstream infection isolates and 33 K. pneumoniae bloodstream infection isolates were collected in 2008 from nine hospitals in Korea. In vitro susceptibility testing and multilocus sequence typing were performed for all isolates. Phylogenetic groupings and distribution of virulence determinants and addiction systems were examined for only E. coli isolates. RESULTS Among the 89 CTX-M-producing E. coli isolates, 54 isolates (60.7%) contained bla(CTx-M-15) and bla(CTx-M-14) was identified in 31 isolates (34.8%). Among 33 CTX-M-producing K. pneumoniae isolates, bla(CTx-M-14) and bla(CTx-M-15) were identified in 18 (54.5%) and 15 (45.5%) isolates, respectively. While CTX-M-14- and CTX-M-15-producing E. coli isolates displayed similar antimicrobial resistance rates, CTX-M-15-producing K. pneumoniae isolates showed significantly higher resistance rates of ciprofloxacin and piperacillin-tazobactam than CTX-M-14-producing isolates. ST131 and ST405 were the main clones in both CTX-M-14- and CTX-M-15-producing E. coli isolates. Although the frequency of virulence determinants was similar between two E. coli groups, ST131 and ST405 isolates producing CTX-M-15 showed higher frequency of determinants. In addition, CTX-M-15-producing E. coli isolates showed higher prevalence of addiction systems, particularly vagCD. ST405 showed the highest prevalence rates among main E. coli clones. In K. pneumoniae, ST15 and ST11, with high resistance rates, were the main clones of CTX-M-15-producing isolates, but no main clones was found among CTX-M-14-producing isolates because of extreme diversity. CONCLUSIONS Rapid increase of CTX-M-15-producing E. coli isolates was due to certain clone with high frequency of virulence determinants and addiction systems. High antimicrobial resistance rates of CTX-M-15-producing K. pneumoniae isolates may contribute to their increase.
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