Multidrug-resistant Extended-spectrum Beta-lactamase Research Articles

Emerging Trends of Extended Spectrum BetaLactamase and Metallo-Beta Lactamase Escherichia Coli Strains among Pregnant Women in Mile 4 Hospital, Abakaliki: Implications for Antenatal Care

This investigation assessed the prevalence of extended spectrum beta-lactamase (ESBL) and metallo-beta lactamase (MBL) producing Escherichia coli among seemingly healthy pregnant women attending the antenatal clinic at Mile 4 Hospital in Abakaliki, Nigeria. A total of 100 midstream urine samples were collected and processed using standard microbiology techniques. Antibiotic susceptibility testing was conducted via the disc diffusion method. ESBL and MBL production screening utilized the double disc synergy test and the combined disc test inhibition assay, respectively. The findings demonstrated a 54% prevalence of E. coli among the study participants, with the highest occurrence observed in the third trimester (31.5%) and the lowest in the first trimester (25.9%). Across age groups, prevalence ranged from 9.3% in participants aged ≤20 years to 44.4% in the 21-30 age bracket. Additionally, among participants with varying educational backgrounds, prevalence ranged from 18.5% in uneducated individuals to 33.3% in those with a secondary education. Antibiotic susceptibility of the isolates varied from 0% to 81.5%. ESBL and MBL screening identified 18 (33.3%) and 11 (20.4%) positive isolates, respectively. The antibiotic susceptibility among ESBL-producing E. coli ranged from 0% to 100%, while MBL-positive E. coli showed susceptibility ranging from 0% to 90.5%. The multiple antibiotic resistance index (MARI) ranged from 0.3 to 1.0, with an average of 0.7 among the isolates. This study highlights a substantial prevalence of multidrug-resistant ESBL and MBL-producing E. coli strains among apparently healthy pregnant women. This situation raises concerns about the early exposure of fetuses to multidrug resistance, emphasizing the urgency for proactive measures to address this emerging health risk. Keywords: ESBL positive E. coli, metallo-betalactamase positive E. coli, apparently healthy pregnant women, Abakaliki, Nigeria.

High Resistance to Antibiotics Recommended in Standard Treatment Guidelines in Ghana: A Cross-Sectional Study of Antimicrobial Resistance Patterns in Patients with Urinary Tract Infections between 2017-2021.

Management of urinary tract infections is challenged by increasing antimicrobial resistance (AMR) worldwide. In this study, we describe the trends in antimicrobial resistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. The proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and carbapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales was the most common group of organisms, E. coli (70.6%) being the most common isolate and Enterococcus spp. the most common gram-positive (1.3%) organisms. Among oral antimicrobials, the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2%) and the least resistance to fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem (0.3%). The highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). Extended-spectrum beta-lactamase (ESBL) positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recommended antimicrobials.

Prevalence and Profiles of Antibiotic Resistance Genes mph(A) and qnrB in Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli Isolated from Dairy Calf Feces.

The use of antibiotics to treat dairy calves may result in multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. This study investigated fluoroquinolone and macrolide resistance genes among ESBL-producing E. coli isolated from dairy calves. Fresh fecal samples from 147 dairy calves across three age groups were enriched to select for ESBL-producing E. coli. Plasmid-mediated fluoroquinolone (qnrB), macrolide (mph(A)), and beta-lactam (blaCTX-M groups 1 and 9) resistance genes were identified by PCR and gel electrophoresis in ESBL-producing E. coli. Beta-lactamase variants and antibiotic resistance genes were characterized for eight isolates by whole-genome sequencing. Seventy-one (48.3%) samples were positive for ESBL-producing E. coli, with 159 (70.4%) isolates identified as blaCTX-M variant group 1 and 67 (29.6%) isolates as blaCTX-M variant group 9. Resistance gene mph(A) was more commonly associated with blaCTX-M variant group 1, while resistance gene qnrB was more commonly associated with variant group 9. E. coli growth was quantified on antibiotic media for 30 samples: 10 from each age group. Significantly higher quantities of ceftriaxone-resistant E. coli were present in the youngest calves. Results indicate the dominant blaCTX-M groups present in ESBL-producing E. coli may be associated with additional qnrB or mph(A) resistance genes and ESBL-producing E. coli is found in higher abundance in younger calves.

Molecular Detection of Carbapenem Resistant Gram Negative Bacterial Isolates from Dogs

Background: Carbapenems are beta-lactam antibiotics that are considered as the last line of therapy against multidrug resistant extended spectrum beta-lactamase. The resistance to carbapenems predominantly through carbapenemase is one of the most important emerging health problems worldwide in the therapy of clinical infections. The objective of the present study is to determine the presence of carbapenemase encoding genes among Gram- negative bacterial spp. associated with clinical infections in dogs. Methods: 30 Escherichia coli, 11 Klebsiella pneumoniae and three Pseudomonas aeruginosa isolated from urine, swabs from lesional skin and anterior vagina of dogs presented with different clinical ailments formed the samples for the study. Polymerase chain reaction was carried out to detect the presence of carbapenemase encoding genes viz., KPC, NDM, OXA, VIM and IMP among the isolates. Result: Out of the 44 Gram- negative isolates tested, 28 (76.3%) were positive for at least one tested carbapenemase gene. The highest frequency of carbapenemase recorded was for NDM followed by OXA-181, KPC, OXA-48 and VIM. Our study identified a high prevalence of carbapenemases among companion animals like dogs which could act as potential source of transmission of these resistance bacteria or their genomes to humans.

Extended-spectrum beta-lactamase (ESBL) producing and multidrug-resistant Escherichia coli in street foods: a public health concern.

Antimicrobial resistance (AMR) pattern and virulence genes of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli from foods of animal origin were evaluated. Based on combination disc method and ESBL E test, 42 of the 213 E. coli isolates were confirmed as ESBL producers where a high presence was observed in raw foods (60.62%), environmental samples (46.73%) and ready to eat foods (42.99%) of which 31(26.49%), 3(6.97%) and 7(15.21%) samples harbored ESBL E. coli, respectively. Higher contamination rates were observed in samples collected from meat vendors (54.36%), milk vendors (48.88%) and egg vendors (45.20%) of which 16.1%, 11.11% and 2.05%, respectively were ESBL E. coli. Among the 42 ESBL isolates, 85.71% (36/42) were multidrug-resistant. On polymerase chain reaction (PCR) analysis, expression of beta-lactamase genes viz., blaCTXM was noted in 69.04% (29/42) ESBL isolates, blaTEM in 66.66% (28/42) and blaOXA-1 in 19.04% (8/42) isolates, while blaSHV was not detected in any of the isolates. Other AMR genes viz., blaAmpC, sul1, sul2, tet(A), tet(B), catI, dhfrI, aac(3)-IIa(aacC2), aph(3')-Ia(aphA1), qnrB, qnrS were detected by PCR in 39, 28, 29, 3, 9, 5, 17, 11, 6, 6 and 33 isolates, respectively. None of the isolates harbored chloramphenicol (floR) and plasmid-mediated quinolone resistance (PMQR) (qnrA) genes. However, 21 isolates were positive for class I integron (int1), 5 for EPEC (eae) and 9 for ETEC (lt) while none were carrying bfp or stII genes. All ESBL producing isolates formed a single group when subjected to enterobacterial repetitive intergenic consensus (ERIC PCR) genotyping. The presence of multidrug-resistant ESBL E. coli in street foods of animal origin raises the issues of food safety and public health.

Phylogenetic Characterization and Multilocus Sequence Typing of Extended-Spectrum Beta Lactamase-Producing Escherichia coli from Food-Producing Animals, Beef, and Humans in Southwest Nigeria

Multidrug-resistant extended-spectrum beta lactamase (ESBL)-producing Escherichia coli strains are emerging globally in both humans and animals. Antimicrobial susceptibility testing and ESBL screening were performed on pure cultures of 216 E. coli isolates from human and animal fecal samples as well as beef. Polymerase chain reaction was performed for the detection of resistance genes. Representative isolates of ESBL-producing E. coli were randomly selected for multilocus sequence typing and pulsed field gel electrophoresis (PFGE). Sixty of the isolates were identified as ESBL producers, and seven resistance genes were amplified in them: TEM (61.7%), blaCTX-M-15 (51.7%), AAC-6-LB (43.3%), blaCTX-M-1 (38.3%), blaCTX-M-9 (33.3%), blaCTX-M-2 (21.7%), and SHV (11.7%); they were classified into four phylogroups: A (25%), B1 (45%), B2 (20%), and D (10%). Thirty of these isolates were clustered into 10 sequence types with ST131 being mostly prevalent. Six PFGE types were discovered, each of which was shared by isolates from different subjects and had the same phylogroups and resistance gene profiles. There was a dissemination of PFGE types across various groups among humans, animals, and beef. This underlines the fact that the spread of ESBL E. coli could be from humans to animals, from animals to humans, as well as across animal species.

Analysis of Bacterial and Fungal Infections after Cytoreduction Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Observational Single-Centre Study.

Introduction While hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreduction surgery (CRS) has been shown to improve patient survival and disease-free progression in peritoneal carcinoma (PC) patients, the procedure relates to a high postoperative infection rate. Herein, we report the bacterial and fungal infections after CRS and HIPEC from a single institution in Saudi Arabia. Patients and Methods A prospective observational study was conducted on 38 patients with PC selected for CRS/HIPEC procedure between 2012 and 2015 in our centre. Results Postoperative bacterial and fungal infection within 100 days was 42.2%, bacterial infection was reported always, and fungal infection was reported in 5 (13.2%) cases. Infections from the surgical site were considered the most common infection site. Multidrug-resistant extended-spectrum beta-lactamase (ESBL) Escherichia coli was the most frequent isolate, followed by multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Lower preoperative albumin and a prolonged preoperative activated partial thromboplastin time (APTT) are associated with postoperative infections, while a prolonged preoperative hospital stay (hazard ratio (HR) = 1.064; confidence interval (CI) = 1.002–1.112; P=0.042) and more intraoperative blood loss (>10%) (HR = 3.919; 95% CI = 1.024–14.995; P=0.046) were independent risk factors for postoperative infections. Three cases died during the follow-up period; all were due to infection. Discussion The infection rate in our centre compared to previous studies of comparable patients was matching. Effective management of postoperative infections should be considered, and identified risk factors in this study can help to focus on effective prevention and treatment strategies.

Tunicate-associated bacteria show a great potential for the discovery of antimicrobial compounds.

Tunicates (Ascidians, sea squirts) are marine protochordates, which live sedentary or sessile in colonial or solitary forms. These invertebrates have to protect themselves against predators and invaders. A most successful strategy, to not being eaten by predators and prevent pathogenic microorganisms to settle, is the usage of chemical molecules for defence. To accomplish this, tunicates take advantage of the specialized metabolites produced by the bacteria associated with them. Therefore, the microbiome of the tunicates can be regarded as a promising bioresource for bacterial strains producing compounds with antibacterial activity. The aim of this study was to test this hypothesis by (i) isolation of tunicate-associated bacteria, (ii) analysis of the antibacterial activities of these strains, and (iii) purification and structure elucidation of an active compound derived from this bioresource. In total, 435 bacterial strains were isolated and thereof 71 (16%) showed antibacterial activity against multidrug resistant (MDR) bacteria. Therefrom, the ethyl acetate crude extracts from liquid fermentations of 25 strains showed activity against MDR Extended-Spectrum Beta-Lactamase (MDR-ESBL) Escherichia coli, MDR Bacillus cereus, Micrococcus luteus, and Bacillus megaterium. Phenotypic analysis based on 16S rDNA sequencing revealed the active strains belonging to different genera and phyla, like Bacillus, Pantoea, Pseudoalteromonas, Salinicola, Streptomyces, Vibrio and Virgibacillus. To obtain first insights into the molecules responsible for the antibacterial activities observed, strain Pseudoalteromonas rubra TKJD 22 was selected for large-scale fermentation and the active compound was isolated. This allowed the purification and structure elucidation of isatin, a compound known for its strong biological effects, thereunder inhibition of Gram-positive and Gram-negative pathogens.

Detection of extended spectrum beta-lactamase producing Gram-negative organisms: hospital prevalence and comparison of double disc synergy and E-test methods

Background and objectives: Emergence of extended spectrum beta-lactamase (ESBL) producing bacteria is a major public health concern. Detection of multi drug resistant (MDR) ESBL producing organisms is necessary to prevent its spread and effective treatment. The purpose of the present study was to determine the magnitude of ESBL producing organism in hospital setting and to compare the suitability of double disc synergy test (DDST) and cefepime-clavulanate E-test method for the detection of ESBL producing organisms in routine microbiology laboratory.Materials and methods: The study was carried out in the Department of Microbiology, Sir Salimullah Medical College, Dhaka from January 2011 to December 2011. Clinical samples included urine and pus from patients with suspected urinary tract and wound infections respectively. Standard microbiological methods were employed for isolation and identification of the organisms. DDST and E-test were used to detect ESBL producing Gram negative organisms.Results: A total of 186 Gram-negative organisms were isolated from various samples. Among the 186 Gram negative bacteria, 120 (64.5%) were Esch. coli while 33 (17.7%), 20 (10.8%) and 11 (5.9%) were Pseudomonas sp, Klebsiella sp and Proteus sp respectively. Out of total 186 isolates, 77 (41.4%) and 73 (39.2%) isolates were found ESBL producers by DDST and E-test method (p=0.674) respectively. Compared to Escherichia coli, Pseudomonas and Proteus, significantly high (p<0.01) proportion of Klebsiella were ESBL positive by both DDST and E-test methods. The detection rate of ESBL producing organisms was not significantly different by DDST and E-test (41.4% vs 39.2%). Non-determinable result was obtained for 4 (2.2%) isolates by E-test method.Conclusion: In our present study, a substantially large number of clinical isolates were found ESBL producers. Compared to E-test, DDST was found as a reliable, convenient and inexpensive method for detection of ESBL producing organism in routine microbiology laboratory practice.IMC J Med Sci 2018; 12(1): 32-36

Low Prevalence of Carbapenem Resistance in Clinical Isolates of Extended Spectrum Beta Lactamase (ESBL) Producing <i>Escherichia coli</i> in North Central, Nigeria

Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli is a global cause of life threatening infections. We determined the presence of ESBL and carbapenemase production in clinical isolates of E. coli and their antibiotic susceptibility. Clinical isolates of community and hospital acquired E. coli from 220 patients seen at a tertiary hospital were evaluated. Antibiotic susceptibility testing was by the modified Kirby-Bauer protocol while ESBL production was determined by the Double Disk Synergy Test (DDST). Carbapenem resistance was confirmed by the Modified Hodge Test. Of the 220 isolates, 122 (55.5%) were from females; 41 (18.6%) were ESBL positive. About 90% of the ESBL producing isolates were resistant to nine of the 15 antimicrobial agents tested. However, only one (2.4%) of the 41 ESBL producing isolates exhibited carbapenem resistance. The ESBL negative isolates were susceptible to Meropenem (100%), Cefepime (97.8%), Ceftriaxone (96.6%) and Cefotaxime (96.6%). All the ESBL producing isolates harbored detectable plasmids with sizes ranging from 2322 to 23,130 base pairs. Our findings show that although multidrug resistant ESBL producing E. coli are prevalent in both the hospital and the community in this environment, carbapenem resistance is still low. We recommend that institutions develop guidelines for the early phenotypic detection of ESBLs and carbapenem resistance.

Prevalence of ESBL phenotype, blaCTX-M-1, blaSHV and blaTEM genes among uropathogenic Escherichia coli isolates from 3 military hospitals of Tehran, Iran

Objective: To determine the extended-spectrum beta-lactamase (ESBL) production and prevalence of blaCTX-M-1, blaSHV and blaTEM genes among uropathogenic Escherichia coli (UPEC) isolates from 3 military hospitals of Tehran during 2015-2016. Methods: One-hundred and eleven isolates were adopted. The antibiotic susceptibility testing was conducted according to Clinical and Laboratory Standards Institute guidelines. The combine disk was used for phenotypic ESBL production. The ceftazidime MIC was conducted with the micro-broth dilution test. The PCR assay was used to detect the blaCTX-M-1, blaSHV and blaTEM genes. Results: In the broth microdilution method, 103 (92.7%) isolates showed minimal inhibitory concentration (MIC) ≥ 1 µg/mL, and also in the combined disk method, 89 (80.1% of all) were ESBL positive. On the other hand, among 91 ceftazidime resistant isolates, 86 (77.4% of all) were ESBL positive. The difference between the two methods for ESBL confirmation was not significant. The result of MIC was similar to the disk diffusion method in the detection of phenotypic ESBL production. Among ESBL producer isolates, the prevalence of blaCTX-M-1, blaSHV and blaTEM was 77.4% (n = 86), 47.4% (n = 53) and 2.4% (n = 2), respectively. These genes were amplified in a wide range MIC of ceftazidime. Conclusions: The prevalence of multi-drug resistant UPEC and ESBL positive isolates was high in military hospitals. The majority of UPEC isolates amplified blaCTX-M-I and blaSHV type β-lactamase genes. One-third of isolates were positive in presence of both these genes. There was no relation between ceftazidime MIC and presence of beta-lactamase genes.

Molecular and phylogenetic characterization of multidrug resistant extended spectrum beta-lactamase producing Escherichia coli isolated from poultry and cattle in Odisha, India

The present study was undertaken to determine the occurrence and characterization of extended spectrum beta-lactamase (ESBL) producing Escherichia coli isolated from cattle and poultry in Odisha, India. Of 316 E. coli isolated from 305 samples (170 fecal samples from poultry and 135 milk samples from cattle), a total of 18 E. coli isolates were confirmed as ESBL producers by combination disc method and ESBL E-test. The isolates were resistant to oxyimino cephalosporins and monobactam as revealed by disc diffusion assay and determination of minimum inhibitory concentration. Resistance against other antibiotics was frequently noted as well. Further, beta-lactamase genes viz., blaSHV, blaCTXM, blaTEM and blaampC were detected in 17, 13, 9 and 2 isolates, respectively in PCR. Of the 18 ESBL strains, 16 were positive for class I integron (int1), nine of them carried sulphonamide resistance gene (sul1) and one harbored quinolone resistance gene (qnrB). Virulence markers for extraintestinal pathogenic E. coli like astA, tsh and iucD were also present in 4, 3 and 3 isolates, respectively. All the PCR amplified products were cloned and subjected to sequencing for homology analysis and data were submitted to gene bank. Sequence analysis of the amplified variable regions of class 1 integron of four representative isolates revealed the presence of aadA2 and dfrA12 gene cassettes conferring resistance to aminoglycosides and trimethoprim, respectively. Most of the ESBL producing strains emerged as single lineage through phylogenetic analysis by RAPD and ERIC PCR. This is the first ever systemic study on multidrug resistant ESBL producing E. coli in food producing animals from India.

Multidrug-Resistance and Extended Spectrum Beta-Lactamase Production in Uropathogenic E. Coli which were Isolated from Hospitalized Patients in Kolkata, India

Urinary Tract Infections (UTIs) are mostly caused by Escherichia coli. The appropriate therapy demands a current knowledge on the antimicrobial susceptibility pattern amongst these pathogens, as an inappropriate use of antibiotics may lead to complications and treatment failure. The UTIs which are caused by multidrug resistant Extended-Spectrum Beta-Lactamase (ESBL) producing bacteria further pose a severe problem, as the treatment options are limited. The aim of this study was to identify the pattern of multi drug resistance amongst the uropathogenic E. coli (UPEC) isolates which were obtained from hospitalized patients. Forty UPEC were isolated from 200 urine samples of hospitalized patients who were clinically suspected for UTIs. Antimicrobial susceptibility screening was performed by using 16 antibiotics, by the Kirby Bauer disk diffusion technique. The isolates which were resistant to the third generation cephalosporins were subjected to the ESBL confirmatory test by using drug and drug-inhibitor combination disks by following the CLSI guidelines. All the 40 isolates except three were multidrug resistant. They showed the highest sensitivities for nitrofurantoin (72.5%) and amikacin (70%). A high level of resistance was observed against ampicillin (97.5%), nalidixic acid and cefelexin (95%), amoxicillin (92.5%), cotrimoxazole (82.5%) and ciprofloxacin (80%) respectively. Thirty different antibiotic resistance patterns were observed against the different antibiotics. Twenty-eight out of the 40 isolates were resistant to the third generation cephalosporins. However, the phenotypic test for the ESBL confirmation indicated that eighteen out of the twenty-eight isolates were ESBL producers and that eleven different drug resistance patterns were observed amongst them. Therefore, this study accounts for the varied multidrug resistance pattern amongst the uropathogenic E. coli which were isolated from hospitalized patients in Kolkata, an eastern region of India. Nitrofurantoin and amikacin should be assigned as potent drugs to treat this infection in this region of the country. These varied resistance patterns present major therapeutic and infection control challenges and they suggest a heterogeneous population of the uropathogenic E. coli isolates which circulate in this sector of India.

Molecular epidemiology of multidrug resistant extended spectrum beta-lactamase producing Klebsiella pneumoniae at a Jamaican hospital, 2000 - 2004

BackgroundThe accurate identification of a pathogen beyond the species level is critical in epidemiological studies and investigations of nosocomial outbreaks of infection. The clonal relatedness of 66 multidrug resistant (MDR) strains of extended spectrum beta-lactamase (ESBL) producing K. pneumoniae isolated from clinical specimens from hospitalized patients at a Jamaican hospital during a 5 year period were determined by pulsed field gel electrophoresis (PFGE).ResultsA total 10 different ESBL producing K. pneumoniae genotypes designated Clones I-X were found. The most frequently occurring strains belonged to Clones I (21/66, 32%), II (15/66, 26%), III (13/66, 20%) and IV (8/66, 12%) which accounted for 86% (57/66) of ESBL producing K. pneumoniae strains over the 5 year period. The remaining 9 (14%) cases of ESBL producing K. pneumoniae were due to strains of Clones V-X. The 4 predominant clones persisted for several years in the hospital.ConclusionsThe clonal and temporal distribution of the MDR ESBL producing K. pneumoniae strains among clinical service areas did not suggest outbreaks of the organism during the period of study. Instead the molecular epidemiology of ESBL producing K. pneumoniae at this hospital was more representative of an endemic persistence of clones of the organism with limited dissemination from patient to patient. Further studies to investigate the factors which determine the emergence and persistence of MDR ESBL producing K. pneumoniae in Jamaican hospitals and their impact on clinical and economic outcomes at such institutions would be useful.

Pharmacodynamic activity of ertapenem versus multidrug-resistant genotypically characterized extended-spectrum -lactamase-producing Escherichia coli using an in vitro model

This study assessed the pharmacodynamic activity of ertapenem against multidrug-resistant (MDR) genotypically characterized extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli using an in vitro model. Six ESBL-producing E. coli with the CTX-M-15 genotype were studied. All six strains were MDR (defined as resistance to third-generation cephalosporins and > or = two other unrelated antimicrobial classes). The in vitro pharmacodynamic model was inoculated with 1 x 10(6) cfu/mL, and ertapenem was dosed once daily at 0 and 24 h to simulate free (f) Cmax and t(1/2) obtained after a standard 1 g intravenous once-daily dose in healthy volunteers (fCmax, 15 mg/L; t(1/2), 4 h). Sampling was performed over 48 h to assess viable growth and resistance selection. Ertapenem T(>MIC) > or = 98% (ertapenem MICs < or = 0.25 mg/L) resulted in bactericidal (> or = 3 log(10) killing) activity at 6, 12, 24 and 48 h against all strains. Eradication of organisms from the in vitro model (below the level of detection) occurred at 2 h followed by slow regrowth of the majority of the strains (5 of 6) over 12, 24 and 48 h time points. Despite limited regrowth, ertapenem achieved a bactericidal effect against all strains (all time points) over the 48 h study period. Ertapenem was rapidly bactericidal (in approximately 2 h) against MDR ESBL (CTX-M-15)-producing E. coli (ertapenem MICs < or = 0.25 mg/L) when simulating free drug after 1 g intravenous once-daily dosing. This bactericidal activity was maintained over the 48 h experimental period with only minor regrowth, which was not associated with MIC increase from baseline.