Extended Spectrum Beta-Lactamase-ProducingKlebsiella pneumoniaeOutbreaks During a Third Generation Cephalosporin Restriction Policy

Abstract Background Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli. Methods This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. Discussion Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024. Trial registration The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.

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Isolation of third generation cephalosporin resistant Enterobacteriaceae from retail meats and detection of extended spectrum beta-lactamase activity

Journal of Microbiological Methods ◽

10.1016/j.mimet.2021.106314 ◽

2021 ◽

Vol 189 ◽

pp. 106314

Author(s):

Mary Rao ◽

Anna Laidlaw ◽

Leo Li ◽

Kristian Young ◽

Sandeep Tamber

Keyword(s):

Generation Cephalosporin ◽

Third Generation ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Retail Meats

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Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00187-16 ◽

2016 ◽

Vol 60 (7) ◽

pp. 4237-4243 ◽

Cited By ~ 24

Author(s):

Danielle M. Zerr ◽

Arianna Miles-Jay ◽

Matthew P. Kronman ◽

Chuan Zhou ◽

Amanda L. Adler ◽

...

Keyword(s):

Relative Risk ◽

Relative Risk Ratio ◽

Adjusted Relative Risk ◽

Third Generation ◽

Beta Lactamase ◽

Antibiotic Exposure ◽

Content Type ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Extended Spectrum

ABSTRACTThe objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producingEscherichia coliorKlebsiella pneumoniaeinfections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producingE. coliorK. pneumoniaeisolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistantE. coliandK. pneumoniaeisolates should include resistance mechanisms when possible.

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Frequency of extended spectrum beta lactamase in E.CoIi and klebsiella pneumoniae in bacterial cultures.

The Professional Medical Journal ◽

10.29309/tpmj/2021.28.09.6097 ◽

2021 ◽

Vol 28 (09) ◽

pp. 1288-1291

Author(s):

Saeeda Nabat ul Hassan ◽

Ghulam Asghar Bhutta ◽

Khushbu Farva

Keyword(s):

Klebsiella Pneumoniae ◽

Generation Cephalosporin ◽

Cross Sectional Study ◽

Diffusion Method ◽

P Value ◽

Beta Lactamase ◽

Cross Sectional ◽

Extended Spectrum Beta Lactamase ◽

Bacterial Cultures ◽

Extended Spectrum

Objective: To determine frequency and pattern of extended spectrum beta lactamase in Klebsiella pneumoniae and E. coli in bacterial cultures. Study Design: Cross Sectional study. Setting: Department of Pathology Sahara Medical College Narowal. Period: January to June 2020. Material & Methods: Total 1100 bacterial isolates were studied out of them 655 E.coli and 445 of klebsiella pneumoniae. All samples were subjected to double disc diffusion method using third generation cephalosporin and amoxacillin-clavulanic acid for detection of ESBL. Data was analyzed using SPSS software version 24, and results were calculated in the form of frequency, percentage and standard deviation. P-value ≤0.05 was taken as statistically non-significant. Results: There were 48.9% male and 51.1% female subjects out of 1100 total cases. E.coli was detected in 59.5% and klebsiella in 40.5% samples. Total 44.2% samples were positive for ESBL enzyme. Of 655 E.coli samples 40.8% and of 445 Klebsiella pneumoniae samples 49.2% were positive for ESBL enzyme. Conclusion: It is necessary to detect ESBL positive Klebsiella pneumoniae and E.coli in laboratory workflow to avoid unnecessary use of antibiotics and development of resistance against them.

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Reduced Use of Third-Generation Cephalosporins Decreases the Acquisition of Extended-Spectrum Beta-Lactamase-ProducingKlebsiella pneumoniae

Infection Control and Hospital Epidemiology ◽

10.1086/502304 ◽

2004 ◽

Vol 25 (10) ◽

pp. 832-837 ◽

Cited By ~ 48

Author(s):

Sang-Oh Lee ◽

Eun Sun Lee ◽

Shin Young Park ◽

Sue-Yun Kim ◽

Yiel-Hae Seo ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Independent Risk Factor ◽

Tertiary Care ◽

Prior Exposure ◽

Third Generation ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Third Generation Cephalosporins

AbstractObjectives:To identify risk factors for the respiratory acquisition of extended-spectrum beta-lactamase (ESBL)-producingKlebsiella pneumoniaeamong patients admitted to a neurosurgical intensive care unit (NSICU) and to modify them without changing general infection control measures.Design:Nested case-control and intervention study.Setting:A 1,200-bed, tertiary-care teaching hospital with a 17-bed NSICU.Methods:Sputa of all patients admitted to the NSICU were cultured weekly during the study. From October 2002 through February 2003, 29 case-patients from whose sputum ESBL-producingK. pneumoniaewas isolated were detected and 59 controls-patients were randomly selected among patients without any positive isolate of ESBL-producingK. pneumoniae.After analyzing the risk factors, we intervened to modify them and compared the acquisition rate of ESBL-producingK. pneumoniaebefore (October 2002 to February 2003) and after (April to August 2003) the intervention.Results:Multivariate analysis showed that prior exposure to third-generation cephalosporins (TGCs) (OR, 6.0; CI95, 1.9 to 18.6;P= .002) was an independent risk factor of ESBL-producingK. pneumoniaeacquisition. The neurosurgical team was notified of the result, and the infectious diseases specialist visited the NSICU three times a week to regulate TGC use during the intervention period. Patients admitted before the intervention were older than patients admitted after. The respiratory acquisition of ESBL-producingK. pneumoniaeper 1,000 patient-days (13.5 [CI95, 8.9 to 18.1] vs 2.7 [CI95, 0.9 to 4.6]) and the antimicrobial use density of TGCs (38.2 ± 5.0 vs 17.3 ± 2.6;P< .001) decreased significantly after the intervention.Conclusion:Prior exposure to TGCs was an independent risk factor for the respiratory acquisition of ESBL-producingK. pneumoniae,and less use of TGCs was associated with a decrease in acquisition.

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Antibiotic Susceptibility Pattern of Extended-Spectrum Beta-Lactamase-Producing Klebsiella Pneumoniae and Escherichia Coli

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v27i3.1634 ◽

2021 ◽

Vol 27 (3) ◽

pp. 282

Author(s):

Erlina Wahyu Elmawati ◽

Dewi Indah Noviana Pratiwi ◽

Noor Muthmainah ◽

Agung Biworo

Keyword(s):

Escherichia Coli ◽

Intensive Care ◽

Klebsiella Pneumoniae ◽

Generation Cephalosporin ◽

Beta Lactamase ◽

Cross Sectional ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Sensitivity Pattern ◽

Using Data

Extended-Spectrum Beta-Lactamase (ESBL) producing bacteria is a type of resistance that leads to complex management of patients in intensive care due to their resistance to first, second, and third-generation Cephalosporin and monobactam antibiotics. The most ESBL-producing bacteria are found in the family Enterobacteriaceae, especially Klebsiella pneumoniae and Escherichia coli. The purpose of this research was to determine the sensitivity pattern of ESBLproducing bacteria in Intensive Care Units (ICUs) of Ulin Hospital, Banjarmasin, in the period of 2016-2018. This research was a descriptive study with a cross-sectional approach using data from the laboratory medical records of patients with positive ESBL in the ICUs of Ulin Hospital, Banjarmasin, between 2016 and 2018. The research sample was taken by the total sampling method. This research obtained 216 isolates of ESBL-producing bacteria consisting of 155 (71.8%) isolates of Klebsiella pneumoniae and 61 (28.2%) Escherichia coli. It was found that the Cephalosporin antibiotics (Cefazolin, Ceftazidime, Ceftriaxone, and Cefepime) and monobactam antibiotic (Aztreonam) had the lowest sensitivity. Aminoglycoside antibiotics (Amikacin), Carbapenem (Ertapenem and Meropenem), and Tetracycline (Tigesycline) were the most sensitive antibiotics. It was concluded that both Klebsiella pneumoniae and Escherichia coli were the most dominant ESBL-producing bacteria and showed good sensitivity to the Amikacin, Ertapenem, Meropenem, and Tigecycline.

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Occurrence of Extended Spectrum Beta-Lactamase Gram-Negative Bacteria from Non-Clinical Sources in Dubai, United Arab Emirates

Water ◽

10.3390/w12092562 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2562

Author(s):

Munawwar A. Khan ◽

Nicola E. Thurgood ◽

Sultan M. Faheem ◽

Naushad Rais ◽

Mohammad Z. Ansari ◽

...

Keyword(s):

United Arab Emirates ◽

Generation Cephalosporin ◽

Fourth Generation ◽

Diffusion Method ◽

Beta Lactamase ◽

Disc Diffusion ◽

M Gene ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Esbl Producers

Extended-spectrum beta-lactamase (ESBL) producing bacteria of the Enterobacteriaceae family are a significant threat to public health, posing a challenge for health authorities worldwide. In the UAE, very little information is available about ESBL producing bacteria from non-clinical sources. In this study, 206 pure cultures belonging to the Enterobacteriaceae family were isolated from food and wastewater sources in Dubai, UAE. All the isolates were tested against third-generation cephalosporin antibiotics by the disc diffusion method and screened on ESBL chromogenic agar. Among all isolates (n = 86), 41.7% were potential ESBL producers belonging to E. coli, Klebsiella, Enterobacter, Shigella, and Citrobacter (KESC group), and Proteus. Of all the potential ESBL producing isolates, 19 (22%) were confirmed as ESBL producers by a double-disc diffusion test with the fourth generation cephalosporin–Cefpirome. The multiplex polymerase chain reaction was used for the detection of ESBL bla genes in the screened isolates. Out of a total of 86 isolates, 52.3% possessed only the blaTEM gene; 39.5% contained both blaTEM and blaSHV genes, while only 3.5% contained the blaCTX-M gene. The carbapenemase resistance test showed eight isolates resistant to imipenem, and only one isolate with metallo-beta-lactamase activity. This study highlights the occurrence of ESBL bla genes among non-clinical isolates from food and wastewater sources in the UAE and emphasizes the importance of food and wastewater surveillance programs in controlling the spread of antibiotic resistance.

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Prevalence of bla CTX M Extended Spectrum Beta Lactamase Gene in Enterobacteriaceae from Critical Care Patients

Journal of Laboratory Physicians ◽

10.4103/0974-2727.86838 ◽

2011 ◽

Vol 3 (02) ◽

pp. 080-083 ◽

Cited By ~ 6

Author(s):

R Indra Priyadharsini ◽

A Kavitha ◽

Reena Rajan ◽

S Mathavi ◽

K R Rajesh

Keyword(s):

Critical Care ◽

Intestinal Flora ◽

Third Generation ◽

Beta Lactamase ◽

M Gene ◽

Extended Spectrum Beta Lactamase ◽

Extended Spectrum ◽

Group I ◽

Third Generation Cephalosporins ◽

Critical Care Patients

ABSTRACT Context: Critical care units provide a favourable environment for the antimicrobial resistant organisms to disseminate. There is recent increase in number of extended spectrum beta lactamase (ESBL) producers because of the emergence of CTX M Beta lactamases produced by Enterobacteriaceae. They colonize the intestinal flora and spread with greater intensity in the community and hospital. Usage of Carbapenems becomes mandatory as the ESBL inhibitor combination antibiotics (Amoxicillin/Clavulanate) are not effective especially against CTX M ESBLs. Aim: The aim of this study is to detect ESBL producing bla CTX M gene in Enterobacteriaceae from infections in Critical care patients and to stress on the intensity of the problem and to make interventions to curb the emergence and dissemination of CTX M ESBLs. Materials and Methods: A total of 118 Enterobacteriaceae isolates from Critical care unit patients were recovered from a variety of clinical specimens. Antimicrobial susceptibility test was done and isolates with resistance or with reduced susceptibility to any of the third generation Cephalosporins were selected for the study. Phenotypic confirmation of ESBL production was done by Double Disc Synergy Test and confirmed by minimum inhibitory concentration. Multiplex polymerase chain reaction was performed to screen the four groups of CTX-M ESBLs. Results: Among the 118 isolates of Enterobacteriaceae 54 isolates were positive for CTX-M group I ESBL which constitutes 45.7 %. Conclusions: Early detection of CTX M producing Enterobacteriaceae by continuous surveillance and thereby reducing their spread and restricted use of third generation Cephalosporins (3GC) antibiotics could be the possible routes to prevent the emergence and spread of CTX M ESBL producing organisms.

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