scholarly journals Activity of cefepime/zidebactam against MDR Escherichia coli isolates harbouring a novel mechanism of resistance based on four-amino-acid inserts in PBP3

2020 ◽  
Vol 75 (12) ◽  
pp. 3563-3567 ◽  
Author(s):  
Sachin S Bhagwat ◽  
Periasamy Hariharan ◽  
Prashant R Joshi ◽  
Snehal R Palwe ◽  
Rahul Shrivastava ◽  
...  

Abstract Background Recent reports reveal the emergence of Escherichia coli isolates harbouring a novel resistance mechanism based on four-amino-acid inserts in PBP3. These organisms concomitantly expressed ESBLs or/and serine-/metallo-carbapenemases and were phenotypically detected by elevated aztreonam/avibactam MICs. Objectives The in vitro activities of the investigational antibiotic cefepime/zidebactam and approved antibiotics (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam and others) were determined against E. coli isolates harbouring four-amino-acid inserts in PBP3. Methods Whole-genome sequenced E. coli isolates (n = 89) collected from a large tertiary care hospital in Southern India (n = 64) and from 12 tertiary care hospitals located across India (n = 25) during 2016–18, showing aztreonam/avibactam MICs ≥1 mg/L (≥4 times the aztreonam epidemiological cut-off) were included in this study. The MICs of antibiotics were determined using the reference broth microdilution method. Results Four-amino-acid inserts [YRIK (n = 30) and YRIN (n = 53)] were found in 83/89 isolates. Among 83 isolates, 65 carried carbapenemase genes [blaNDM (n = 39), blaOXA-48-like (n = 11) and blaNDM + blaOXA-48-like (n = 15)] and 18 isolates produced ESBLs/class C β-lactamases only. At least 16 unique STs were noted. Cefepime/zidebactam demonstrated potent activity, with all isolates inhibited at ≤1 mg/L. Comparator antibiotics including ceftazidime/avibactam and imipenem/relebactam showed limited activities. Conclusions E. coli isolates concurrently harbouring four-amino-acid inserts in PBP3 and NDM are an emerging therapeutic challenge. Assisted by the PBP2-binding action of zidebactam, the cefepime/zidebactam combination overcomes both target modification (PBP3 insert)- and carbapenemase (NDM)-mediated resistance mechanisms in E. coli.

2020 ◽  
Author(s):  
Kun Chen ◽  
Guoliang Yang ◽  
Wenping Li ◽  
Mingcheng Li

Abstract Background:Concerns are increasing over the importance of the hospital intensive care units (ICU) for the transmission of extended spectrum-β-lactamase (ESBLs) -producing Enterobacteriaceae. We reported the clinical characteristics and epidemiology of ESBLs isolates collected from a tertiary care hospital in China. Methods:Escherichia coli(E. coli)and Enterobacter cloacae (E. cloacae)isolates from ICU infection samples were isolated and identified. Antimicrobial susceptibility profiles and production of ESBLs were determined by using the disk diffusion method and the broth microdilution method. Clonality of isolates was determined by ERIC-PCR techniques. Results:From the included the 223 strains isolated from hospitalized patients with nosocomial infections in ICU during 2016 to 2018, the majority of isolates belonged to Gram-negative Enerobacteriaceae including E. coli (46.6% of all strains), and E. cloacae (46.2% of all strains). 63.25% of samples were separated from sputum or tracheal secretions. All of 207 isolates, ESBL-screen positive E. coli was 45.2% (47/104), and 44.7% (46/103) for E. cloacae. Resistance rates of ESBLs-producing E. coli and E. cloacae isolates were 95.5%-91.3% for ampicillin, 80.6%-76.1% for ampicillin/azobactam, 88.1%-28.3% for ciprofloxacin, 89.6%-15.2% for levofloxacin, 34.3%-45.7% for netilmicin, 82.1%-41.3% for compound sulfamethoxazole, 20.9%-43.5% for amikacin, 58.2%-37.0% for gentamicin, 20.9%-69.6% for piperacillin/tazobactam. All of ESBLs-producer isolates resistant to cefazolin, cefuroxime, ceftazidime, ceftriaxone, cefepime in additon to aztreonam were 100%, whereas the susceptibilities of isolates to imipenem and meropenem were 100%. Results of ERIC-PCR in all of ESBLs-producing E. coli isolates exhibited 11 distinct patterns using a similarity coefficient of 0.8. And one distinct ERIC profiles were observed amongst 46 strains of ESBLs-producing E. cloacae. ERIC profiles demonstrated an outbreak of nosocomial infection and ESBLs-producing E. coli and E. cloacae prevalent in the ICU of this hospital.Conclusions:Our data indicate that the ESBLs-producing E. coli and E. cloacae clones are circulating in the ICU and constitute a major source for further disseminating in this hospital. It is necessary to increase surveillance and development of adequate prevention strategies.


2020 ◽  
Author(s):  
Baoguang Liu ◽  
Xiaoling Yuan ◽  
Yiheng Chen ◽  
Xiaoshen Li ◽  
Ming Bai ◽  
...  

Abstract Background The spread of ESBLs-producing bacteria has been strikingly rapid in many regions of the world and it causes therapeutic difficulties in everyday practice. The aims of this study were to investigate the prevalence and susceptibilities of ESBLs-producing Escherichia coli isolates from healthy Tibetan yaks in China, to evaluate the activity of drug combinations on ESBLs-producing E. coli isolates. Methods From July 2018 to August 2019, a total of 750 nasal swab samples were tested for the presence of E. coli and ESBLs-producing strains. The MICs of 11 antimicrobial agents alone and combinations with sulbactam, EDTA or sulbactam-EDTA against 240 ESBLs-producing E.coli strains were determined by the broth microdilution method. Results Overall, 59.87% (n = 449) of the samples were positive for E. coli, 240 (53.45%) of 449 E. coli isolates were confirmed to be ESBLs-producing. The addition of sulbactam to the third generation cephalosporins, amikacin and fosfomycin for all isolates resulted in low MICs, increasing the level of susceptibility from 0, 0 and 0% to 50 ~ 87.5, 4.2 and 100% respectively. The addition of EDTA to fluoroquinolones, doxycycline, florfenicol, amikacin and fosfomycin, showed improved activities and resulted in low MICs, increasing the level of susceptibility from 0, 0, 8.3, 0 and 0% to 4.2 ~ 29.2, 33.3, 33.3, 66.7 and 45.8%, respectively. All other antibacterials (except fluoroquinolones, doxycycline and florfenicol), when combined with sulbactam-EDTA, were found to be more active than combinations only with sulbactam or with EDTA against most of isolates, with lower MIC50s and MIC90s. Conclusion In conclusion, ESBLs-producing E. coli isolates were widespread in healthy Tibetan yaks in China. ESBLs-producing E. coli isolates exhibited varying degrees of multidrug resistance. This study these findings suggested that sulbactam can enhance activity of β-lactams and some non-β-lactams of antimicrobial agents and had a synergistic effects with EDTA in improving activities of some families of antimicrobials.


2020 ◽  
Vol 83 (7) ◽  
pp. 1261-1267
Author(s):  
TING LIU ◽  
JINGFAN WANG ◽  
XIAOMAN GONG ◽  
XIAOXIA WU ◽  
LIU LIU ◽  
...  

ABSTRACT The purpose of the present study was to determine the bioactive compounds in rosemary essential oil (REO) and tea tree essential oil (TEO) and to investigate their antibacterial and antibiofilm activities against Staphylococcus aureus and Escherichia coli in vitro. The MIC and MBC assays were performed to assess the antibacterial activity of these two EOs against S. aureus and E. coli with the broth microdilution method. A crystal violet assay was used to ascertain the effects of EOs on the biofilm formation of the test strains, and a tetrazolium bromide (MTT) assay was used to measure the level of inactivation of mature biofilms by EOs. Gas chromatography–mass spectrometry revealed 15 compounds in REO and 27 compounds in TEO, representing 97.78 and 98.13% of the total EO, respectively. Eucalyptol and α-pinene were found in high concentrations in REO, and the two major compounds in TEO were 4-terpineol and terpinolene. The MICs of REO for the two S. aureus and E. coli test strains were both 0.5 mg/mL, and the MICs of TEO for the two strains were both 0.25 mg/mL. Therefore, these EOs can significantly inhibit the formation of biofilms and induced morphological biofilm changes, as verified by scanning electron microscopy. Both EOs had destructive effects on the mature biofilm of the two test strains. TEO was more inhibitory than REO for biofilm formation by the two test strains. HIGHLIGHTS


2015 ◽  
Vol 57 (3) ◽  
pp. 185-191 ◽  
Author(s):  
Ralciane de Paula MENEZES ◽  
Joseane Cristina FERREIRA ◽  
Walkiria Machado de SÁ ◽  
Tomaz de Aquino MOREIRA ◽  
Lucivânia Duarte Silva MALVINO ◽  
...  

Infections by Candida species are a high-impact problem in public health due to their wide incidence in hospitalized patients. The goal of this study was to evaluate frequency, susceptibility to antifungals, and genetic polymorphism of Candida species isolated from clinical specimens of hospitalized patients. The Candida isolates included in this study were obtained from blood cultures, abdominal fluids, and central venous catheters (CVC) of hospitalized patients at the Clinical Hospital of the Federal University of Uberlândia during the period of July 2010 - June 2011. Susceptibility tests were conducted by the broth microdilution method. The RAPD-PCR tests used employed initiator oligonucleotides OPA09, OPB11, and OPE06. Of the 63 Candida isolates, 18 (28.5%) were C. albicans, 20 (31.7%) were C. parapsilosis complex species, 14 (22.2%) C. tropicalis, four (6.4%) C. glabrata, four (6.4%) C. krusei, two (3.3%) C. kefyr, and one (1.6%) C. lusitaniae. In vitro resistance to amphotericin B was observed in 12.7% of isolates. In vitro resistance to azoles was not detected, except for C. krusei. The two primers, OPA09 and OPB11, were able to distinguish different species. Isolates of C. albicans and C. parapsilosis complex species presented six and five clusters, respectively, with the OPA09 marker by RAPD-PCR, showing the genetic variability of the isolates of those species. It was concluded that members of the C. parapsilosis complex were the most frequent species found, and most isolates were susceptible to the antifungals amphotericin B, flucozanole, and itraconazole. High genetic polymorphisms were observed for isolates of C. albicans and C. parapsilosis complex species, mainly with the OPA09 marker.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Mahoko Ikeda ◽  
Tatsuya Kobayashi ◽  
Fumie Fujimoto ◽  
Yuta Okada ◽  
Yoshimi Higurashi ◽  
...  

Abstract Background Although Escherichia coli is the most frequently isolated microorganism in acute biliary tract infections with bacteremia, data regarding its virulence are limited. Results Information on cases of bacteremia in acute biliary tract infection in a retrospective study was collected from 2013 to 2015 at a tertiary care hospital in Japan. Factors related to the severity of infection were investigated, including patient background, phylogenetic typing, and virulence factors of E. coli, such as adhesion, invasion, toxins, and iron acquisition. In total, 72 E. coli strains were identified in 71 cases, most of which primarily belonged to the B2 phylogroup (68.1%). The presence of the iutA gene (77.3% in the non-severe group, 46.4% in the severe group, P = 0.011) and the ibeA gene (9.1% in the non-severe group, and 35.7% in the severe group, P = 0.012) was significantly associated with the severity of infection. Among the patient characteristics, diabetes mellitus with organ involvement and alkaline phosphatase were different in the severe and non-severe groups. Conclusions We showed that bacteremic E. coli strains from acute biliary tract infections belonged to the virulent (B2) phylogroup. The prevalence of the iutA and ibeA genes between the two groups of bacteremia severity was significantly different.


2015 ◽  
Vol 59 (6) ◽  
pp. 3059-3065 ◽  
Author(s):  
C. Pitart ◽  
F. Marco ◽  
T. A. Keating ◽  
W. W. Nichols ◽  
J. Vila

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S310-S311 ◽  
Author(s):  
Olga Lomovskaya ◽  
Jill Lindley ◽  
Debora Rubio-Aparicio ◽  
Kirk J Nelson ◽  
Mariana Castanheira

Abstract Background QPX7728 (QPX) is a novel broad-spectrum boron-containing inhibitor of serine- and metallo-β-lactamases (MBLs). We evaluated the in vitro activity of QPX combined with several β-lactams against carbapenem-resistant AB (CRAB) and PSA clinical isolates with varying β-lactam resistance mechanisms. Methods A total of 503 CRAB (meropenem [MEM] MIC ≥8 µg/mL) and 762 PSA clinical isolates were tested by the reference broth microdilution method against β-lactams alone and combined with QPX (4 µg/mL and 8 µg/mL). PSA isolates were selected to represent the normal distribution of MEM, ceftazidime–avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance according to 2017 surveillance data (representative panel). Additionally, 262 PSA isolates that were either nonsusceptible (NS) to MEM (MIC, ≥4 µg/mL) or to TOL-TAZ (MIC, ≥8 µg/mL), or resistant (R) to CAZ-AVI (MIC, ≥16 µg/mL) (challenge panel) were also tested. Within this 262 strain challenge set, 56 strains carried MBLs and the majority also had nonfunctional OprD. Results Against CRAB, QPX at 4 and 8 µg/mL increased the potency of all β-lactams tested. MEM-QPX was the most potent combination (table) displaying MIC50/MIC90 at 1/8 and 0.5/4 µg/mL with QPX at fixed 4 and 8 µg/mL, respectively. Susceptibility (S) to MEM was restored in >95% of strains. Against the 500 PSA from the representative panel, S for all QPX combinations was >90%. For the challenge panel, TOL-QPX and piperacillin (PIP)-QPX were the most potent combinations, restoring S in 76–77% of strains. TOL-QPX and MEM-QPX or cefepime (FEP)-QPX restored the MIC values to S rates when applying the CLSI breakpoint for the compound alone (comparison purposes only) in ~90% and ~75% of non-MBL-producing strains, respectively, vs. 60–70% for TOL-TAZ and CAZ-AVI. PIP-QPX reduce the MIC values to S values for PIP-TAZ in ~60% of MBL-producing strains vs. 20–30% and 3–7% for other QPX combinations and non-QPX tested combinations, respectively. Conclusion Combinations of QPX with various β-lactam antibiotics displayed potent activity against CRAB and resistant PSA isolates and warrant further investigation. Disclosures All authors: No reported disclosures.


Author(s):  
Yamuna Devi Bakthavatchalam ◽  
Abirami Shankar ◽  
Rajeshwari Muniyasamy ◽  
John Victor Peter ◽  
Zervos Marcus ◽  
...  

Abstract Objectives Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoquinolizine fluoroquinolones, recently approved in India for the treatment of acute bacterial skin and skin structure infections with concurrent bacteraemia and diabetic foot infections. Ahead of its market launch, the present study aimed to assess the in vitro activity of levonadifloxacin against contemporary Staphylococcus aureus isolates collected from a large tertiary care hospital in India. Additionally, levonadifloxacin activity was tested against hVISA and Bengal Bay clone MRSA isolates. Methods Non-duplicate S. aureus (n = 793) isolates collected at Christian Medical College hospital, Vellore, India during 2013–19 were included in the study. MRSA isolates were identified using a cefoxitin disc diffusion assay. MICs of levonadifloxacin and comparator antibiotics were determined using the broth microdilution method. Mutations in QRDRs were identified for selected levofloxacin-non-susceptible isolates. MLST profiling was undertaken to detect the Bengal Bay clone. Results Among the 793 isolates, 441 (55.6%) were MRSA and 626 (78.9%) were non-susceptible to levofloxacin. Levonadifloxacin showed MIC50 and MIC90 values of 0.25 and 0.5 mg/L, respectively, for all S. aureus, which included hVISA and Bengal Bay clone MRSA. The potency of levonadifloxacin was 16 times superior compared with levofloxacin. Conclusions The present study demonstrated potent activity of levonadifloxacin against contemporary S. aureus isolates, which included MRSA isolates, hVISA isolates, Bengal Bay clone isolates and a high proportion of quinolone-non-susceptible isolates. The potent activity of levonadifloxacin observed in this study supports its clinical use for the treatment of S. aureus infections.


Author(s):  
Anubhuti Khare ◽  
Saroj Kothari ◽  
Vaibhav Misra

Background: Antimicrobial resistance is a serious problem worldwide and differs from region to region. This study was planned to determine the incidence and sensitivity pattern of Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) in our region and discuss the general issues related to antimicrobial resistance.Methods: Prospective study was carried out between March to October 2015. Samples of urine, blood, pus, CSF and miscellaneous samples (fluids, swabs, sputum and stool) were collected from indoor and outdoor patients for isolation and antimicrobial susceptibility of K. pneumoniae, E. coli and P. aeruginosa in the Department of Microbiology G.R. Medical College, Gwalior (MP).Results: Out of the 5000 samples analyzed 1684 showed growth. K. pneumoniae (38.50%), E. coli (33.29%) and P. aeruginosa (28.19%) constituited a total of 805 isolates. Both E.coli and K. pneumoniae showed highest sensitivity for doxycycline (75%; 67% resp.) and second highest for levofloxacin (70%; 64% resp.), whereas, P. aeruginosa showed highest 57% sensitivity for amikacin followed by 48% for levofloxacin. β-lactam antibiotics and aminoglycosides showed high mean resistance (K.pneumoniae-83%, E.coli-79%, P. aeruginosa-86.4%) and (K. pneumoniae-75%, E. coli-61%, P. aeruginosa-70%) resp.Conclusions: The data indicates high resistance among the gram-negative bacteria for β-lactam and aminoglycoside antibiotics. Increasing resistance to doxycycline and flouroquinolones for K. pneumoniae and E. coli and multidrug resistance to P. aeruginosa is a cause of concern in this region. Thus, there is a need to stop misuse of antibiotics with immediate effect and to implement a strong antimicrobial stewardship program.


2020 ◽  
pp. jim-2020-001573
Author(s):  
Sanjida Jahan ◽  
Heather Davis ◽  
Deborah S Ashcraft ◽  
George A Pankey

Pseudomonas aeruginosa is a nosocomial pathogen containing various resistance mechanisms. Among them, metallo-β-lactamase (MBL)–producing Pseudomonas are difficult to treat. Fosfomycin is an older antibiotic that has recently seen increased usage due to its activity against a broad spectrum of multidrug-resistant organisms. Our aim was to evaluate the combination of fosfomycin and meropenem against 20 MBL-producing P. aeruginosa (100% meropenem-resistant and 20% fosfomycin-resistant) using both an Etest minimal inhibitory concentration (MIC): MIC method and time-kill assay. MICs for fosfomycin and meropenem were determined by Etest and by broth microdilution method for the latter. The combination demonstrated synergy by Etest in 3/20 (15%) isolates and 5/20 (25%) isolates by time-kill assay. Results from the Etest method and time-kill assay were in agreement for 14/20 (70%) of isolates. No antagonism was found. Comparing both methods, Etest MIC: MIC method may be useful to rapidly evaluate other antimicrobial combinations.


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