scholarly journals 1106. Evaluation of Penetration of Cefiderocol into Cerebrospinal Fluid Using a Rat Meningitis Model

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S645-S645
Author(s):  
Miki Takemura ◽  
Sachi Kanazawa ◽  
Naoki Kohira ◽  
Yuki Aoe ◽  
Atsushi Morimoto ◽  
...  

Abstract Background Central nervous system (CNS) infections caused by Gram-negative bacteria (GNB) are sometimes hard to treat due to antibiotic resistance and difficulty with penetration into cerebrospinal fluid (CSF). Cefiderocol (CFDC) which was approved by the FDA and the EMA in 2019 to 2020 is a siderophore cephalosporin with potent activity against various GNB including carbapenem-resistant strains. In this study, we evaluated the penetration of CFDC into CSF using a rat meningitis model. Methods To induce meningitis, the anesthetized immunocompetent rats were infected by intracisternal inoculation of a bacterial suspension of 8.7×101 CFU of E. coli SR200138. 200 mg/kg or 50 mg/kg of CFDC was administered via tail vein bolus injection to uninfected rats (n=4/sampling point) and rats with meningitis (n=4/sampling point) 24 hours after infection. CSF was collected by cisternal puncture and blood was collected from heart. The samplings were performed 0.25, 0.5, 1, 3, and 5 hours after dosing. The concentrations of CFDC in plasma and CSF for individuals were determined by LC/MS/MS. PK parameters for the average values in plasma and CSF were calculated. Results CFDC concentration and the PK parameters are shown in Figure and Table, respectively. The penetration of CFDC from plasma to CSF was observed in both uninfected and meningitis groups, and the penetration rates increased in the rats withs meningitis (AUCCSF/AUCplasma: 0.149-0.183) compared with the uninfected rats (AUCCSF/AUCplasma: 0.0508-0.0588). The penetration rates of CFDC in the meningitis were comparable to those of piperacillin, cefepime, and meropenem in human (0.32, 0.103, and 0.39 in strongly inflamed meninges, respectively) [1]. In both groups, elimination of CFDC from CSF was slower compared with that from plasma as seen with other β-lactam antibiotics such as meropenem, suggesting that T> MIC, an indicator that correlates with the efficacy of β-lactams, may be higher in CSF [2]. Table. PK Parameters of Cefiderocol after Intravenous Bolus Administration in Uninfected Rats and Rats with Meningitis Figure. Concentrations of Cefiderocol after Intravenous Bolus Administration in Uninfected Rats and Rats with Meningitis Conclusion It was confirmed that CFDC penetrates into CSF from plasma in a rat model and the penetration rate was increased 3-fold in meningitis. References 1. Nau, R. et al. Clin Microbiol Rev. 2010 Oct;23(4):858–883. 2. Nau, R. et al. Antimicrob Agents Chemother. 1998 Aug;42(8):2012–2016. Disclosures Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Sachi Kanazawa, PhD, Shionogi & Co., Ltd. (Employee) Naoki Kohira, PhD, Shionogi & Co., Ltd. (Employee) Yuki Aoe, BS, Shionogi TechnoAdvance Research Co., Ltd. (Employee) Atsushi Morimoto, n/a, Shionogi TechnoAdvance Research Co., Ltd. (Employee) Kana Horiuchi, MPharm, Shionogi & Co., Ltd. (Employee) Yuji Inoue, MPharm, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi (Employee)

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.


1998 ◽  
Vol 61 (10) ◽  
pp. 1390-1395 ◽  
Author(s):  
JOHN A. LOPES

Acid anionic sanitizers for treatment of fruits and vegetables were prepared using ingredients generally recognized as safe by the U.S. Food and Drug Administration or anionic surfactants and organic acid food additives. They met the regulatory definition as sanitizers by showing bactericidal efficacy of 99.999% in 30 s against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229. These sanitizers showed a broad spectrum of microbicidal activity against both gram-positive and gram-negative bacteria. Antibiotic-sensitive and resistant strains of Listeria monocytogenes and Salmonella typhimurium were equally susceptible to these sanitizers. The acid anionic sanitizers showed microbicidal efficacy equal to that of hypochlorite against Aeromonas hydrophila, E. coli O157:H7, L. monocytogenes, Pseudomonas aeruginosa, S. typhimurium, and S. aureus. Unlike most other sanitizers, these agents do not covalently react with organic components of food; unlike cationic agents, they do not leave residues. The acid anionic sanitizers are prepared using stable, biodegradable, and nontoxic ingredients. Rapid microbicidal activity and the ease of storage, transportation, and use make these sanitizers an attractive alternative to hypochlorite for sanitizing fruits and vegetables.


Author(s):  
Yasmine H. Tartor ◽  
Rasha M. A. Gharieb ◽  
Norhan K. Abd El-Aziz ◽  
Hend M. El Damaty ◽  
Shymaa Enany ◽  
...  

A major increase of bacterial resistance to colistin, a last-resort treatment for severe infections, was observed globally. Using colistin in livestock rearing is believed to be the ground of mobilized colistin resistance (mcr) gene circulation and is of crucial concern to public health. This study aimed to determine the frequency and virulence characteristics of colistin-resistant Gram-negative bacteria from the milk of mastitic cows and raw unpasteurized milk in Egypt. One hundred and seventeen strains belonging to Enterobacteriaceae (n = 90), Pseudomonas aeruginosa (n = 10), and Aeromonas hydrophila (n = 17) were screened for colistin resistance by antimicrobial susceptibility testing. The genetic characteristics of colistin-resistant strains were investigated for mcr-1–9 genes, phylogenetic groups, and virulence genes. Moreover, we evaluated four commonly used biocides in dairy farms for teat disinfection toward colistin-resistant strains. Multidrug-resistant (MDR) and extensive drug-resistant (XDR) phenotypes were detected in 82.91% (97/117) and 3.42% (4/117) of the isolates, respectively. Of the 117 tested isolates, 61 (52.14%) were colistin resistant (MIC >2 mg/L), distributed as 24/70 (34.29%) from clinical mastitis, 10/11 (90.91%) from subclinical mastitis, and 27/36 (75%) from raw milk. Of these 61 colistin-resistant isolates, 47 (19 from clinical mastitis, 8 from subclinical mastitis, and 20 from raw milk) harbored plasmid-borne mcr genes. The mcr-1 gene was identified in 31.91%, mcr-2 in 29.79%, mcr-3 in 34.04%, and each of mcr-4 and mcr-7 in 2.13% of the colistin-resistant isolates. Among these isolates, 42.55% (20/47) were E. coli, 21.28% (10/47) A. hydrophila, 19.12% (9/47) K. pneumoniae, and 17.02% (8/47) P. aeruginosa. This is the first report of mcr-3 and mcr-7 in P. aeruginosa. Conjugation experiments using the broth-mating technique showed successful transfer of colistin resistance to E. coli J53-recipient strain. Different combinations of virulence genes were observed among colistin-resistant isolates with almost all isolates harboring genes. Hydrogen peroxide has the best efficiency against all bacterial isolates even at a low concentration (10%). In conclusion, the dissemination of mobile colistin resistance mcr gene and its variants between MDR- and XDR-virulent Gram-negative isolates from dairy cattle confirms the spread of mcr genes at all levels; animals, humans, and environmental, and heralds the penetration of the last-resort antimicrobial against MDR bacteria. Consequently, a decision to ban colistin in food animals is urgently required to fight XDR and MDR bacteria.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S756-S756
Author(s):  
Helio S Sader ◽  
Michael D Huband ◽  
Cecilia G Carvalhaes ◽  
Mariana Castanheira

Abstract Background Rapidly introducing appropriate antimicrobial therapy is crucial to reduce morbidity and mortality of patients hospitalized with pneumonia (PHP), and therapy is determined mostly by understanding causative pathogens. Ceftazidime–avibactam (CAZ-AVI) was recently approved and ceftolozane–tazobactam (C-T) is in late-stage clinical development for treating nosocomial pneumonia, including ventilator-associated. Methods Bacterial isolates were consecutively collected from PHP (1/patient) in 67 US medical centers in 2018 and the Gram-negative bacilli (GNB) were tested by reference broth microdilution methods for susceptibility (S) to CAZ-AVI, C-T, and many comparators at a central laboratory. Results The most common organisms isolated from PHP were S. aureus (27.0%), P. aeruginosa (PSA) (24.6%), K. pneumoniae (KPN; 7.6%), E. coli (6.8%), S. marcescens (5.4%), and S. maltophilia (XM; 4.5%). Colistin (99.7%S), CAZ-AVI (95.7%S), and C-T (94.9%S) were the most active compounds against PSA; CAZ-AVI (99.9%S), amikacin (AMK; 98.8%S), and meropenem (MEM; 97.6%S) were the most active compounds against Enterobacterales (ENT). CAZ-AVI and C-T retained activity against PSA isolates non-S (NS) to piperacillin–tazobactam (PIP-TAZ), MEM, and cefepime (FEP), whereas PSA isolates NS to PIP-TAZ, MEM, or FEP exhibited low S rates to PIP-TAZ (≤ 39.2%), MEM (≤ 37.8%), and FEP (≤ 38.0%; Table). CAZ-AVI and tigecycline were the only compounds with good activity against carbapenem-resistant ENT (CRE), both with 96.6%S. Among ENT, the most common ESBL and carbapenemase were CTX-M-15 (73%) and KPC-2/3 (76%), respectively. CAZ-AVI was active against all ESBL producers (100.0%S), whereas the S rate to C-T was 82.4%. The most active compounds against multidrug-resistant (MDR) ENT were CAZ-AVI (98.9%S), AMK (91.5%S), and MEM (80.8%S). XM and A. baumannii exhibited low S rates to most antimicrobials tested. Conclusion Gram-negative bacteria were isolated from 70% of PHP, and PSA and ENT represented >80% of these organisms. CAZ-AVI and C-T showed similar coverage (%S) against PSA (95.7–94.9%S). In contrast, C-T was less active than CAZ-AVI against ENT in general and exhibited limited activity against ENT-resistant subsets. Disclosures All authors: No reported disclosures.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Axel B. Janssen ◽  
Toby L. Bartholomew ◽  
Natalia P. Marciszewska ◽  
Marc J. M. Bonten ◽  
Rob J. L. Willems ◽  
...  

ABSTRACT Infections by multidrug-resistant Gram-negative bacteria are increasingly common, prompting the renewed interest in the use of colistin. Colistin specifically targets Gram-negative bacteria by interacting with the anionic lipid A moieties of lipopolysaccharides, leading to membrane destabilization and cell death. Here, we aimed to uncover the mechanisms of colistin resistance in nine colistin-resistant Escherichia coli strains and one Escherichia albertii strain. These were the only colistin-resistant strains of 1,140 bloodstream Escherichia isolates collected in a tertiary hospital over a 10-year period (2006 to 2015). Core-genome phylogenetic analysis showed that each patient was colonized by a unique strain, suggesting that colistin resistance was acquired independently in each strain. All colistin-resistant strains had lipid A that was modified with phosphoethanolamine. In addition, two E. coli strains had hepta-acylated lipid A species, containing an additional palmitate compared to the canonical hexa-acylated E. coli lipid A. One E. coli strain carried the mobile colistin resistance (mcr) gene mcr-1.1 on an IncX4-type plasmid. Through construction of chromosomal transgene integration mutants, we experimentally determined that mutations in basRS, encoding a two-component signal transduction system, contributed to colistin resistance in four strains. We confirmed these observations by reversing the mutations in basRS to the sequences found in reference strains, resulting in loss of colistin resistance. While the mcr genes have become a widely studied mechanism of colistin resistance in E. coli, sequence variation in basRS is another, potentially more prevalent but relatively underexplored, cause of colistin resistance in this important nosocomial pathogen. IMPORTANCE Multidrug resistance among Gram-negative bacteria has led to the use of colistin as a last-resort drug. The cationic colistin kills Gram-negative bacteria through electrostatic interaction with the anionic lipid A moiety of lipopolysaccharides. Due to increased use in clinical and agricultural settings, colistin resistance has recently started to emerge. In this study, we used a combination of whole-genome sequence analysis and experimental validation to characterize the mechanisms through which Escherichia coli strains from bloodstream infections can develop colistin resistance. We found no evidence of direct transfer of colistin-resistant isolates between patients. The lipid A of all isolates was modified by the addition of phosphoethanolamine. In four isolates, colistin resistance was experimentally verified to be caused by mutations in the basRS genes, encoding a two-component regulatory system. Our data show that chromosomal mutations are an important cause of colistin resistance among clinical E. coli isolates.


2015 ◽  
Vol 23 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Alexandru Rafila ◽  
Daniela Talapan ◽  
Olga Mihaela Dorobăţ ◽  
Gabriel Adrian Popescu ◽  
Daniela Piţigoi ◽  
...  

Abstract Introduction: Hospital-acquired infections caused by Enterobacteriaceae producing different types of carbapenem- hydrolizing enzymes are now commonly observed and represent a great limitation for antimicrobial therapy. The purpose of the study was to evaluate the emergence of carbapenem-resistant Enterobaceriaceae among the strains isolated from hospitalized patients to the National Institute of Infectious Diseases, Bucharest (NIID) and the identification of different types of carbapenemases, using phenotypic methods. Materials and methods: Between January - June 2014, 587 strains of Klebsiella pneumoniae, Enterobacter species and E.coli were isolated from various clinical specimens. We were included all non-susceptible strains to carbapenems, according to EUCAST 2014 clinical breakpoints, as determined by using microdilution MicroScan Panels (Siemens Healthcare Diagnostics). The modified Hodge test (MHT) was performed as phenotypic confirmatory test for carbapenemase production according to CLSI guidelines and the combination disk test (KPC, MBL , OXA-48 Confirm kit, Rosco Diagnostica) according to EUCAST guidelines. Results: A total of 45 non-repeat Enterobaceriaceae (32 strains Klebsiella pneumoniae, 5 strains E.coli, 8 strains Enterobacter spp) were identified as non-susceptibile to one or more carbapenems (93,33% ertapenem, 53,33% meropenem, 48,88% imipenem). Most strains were isolated from urine (75,55%). MHT was positive in 55,6% (25/45) of carbapenem-resistant strains; in 24 cases the carbapenem-hydrolizing enzyme was identified as: OXA-48-like (n=16), KPC (n=4), MBL (n=1), KPC + MBL (n=2) and MBL + OXA-48-like (n=1). All carbapenemase- positive strains were 100% resistant to 3rd and 4th generation cephalosporins, showing less resistance to tigecycline (12,5% resistant and 25% intermediate), colistin (37,5%) and fosfomycin (41,6%). Conclusion: During 6 months period, there were isolated 7,66% (45/587) carbapenem-resistant Enterobacteriaceae (K. pneumoniae 21,47%, E. coli 1,23%). Twenty four strains were carbapenemase-producers. The most frequent carbapenemase isolated in our study was OXA-48-like.


Author(s):  
Thresia . ◽  
Surya Sankar ◽  
Siju Joseph ◽  
V.R. Ambily ◽  
Anu Bosewell ◽  
...  

Background: Antibiotic resistance is an emerging concern in the therapy of clinical infections worldwide. Previous studies conducted in our laboratory have confirmed an increase in the prevalence of extended spectrum beta-lactamase (ESBL) among the Gram-negative bacterial pathogens associated with dogs, which could act as a potential source for the transfer of these resistant pathogens or their genetic determinants to human. Since carbapenems are the last resort drugs against these resistant pathogens, the study was aimed to isolate and characterise carbapenem resistance among Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa) associated with common clinical infections in dogs.Methods: A total of 100 samples were collected from lesional skin, urine and anterior vagina of dogs presented to the Veterinary Hospitals of Kerala Veterinary and Animal Sciences University at Mannuthy and Thrissur. The samples were cultured onto Brain Heart Infusion Agar (BHIA), Eosin Methylene Blue (EMB) and Mac Conkey (MAC) for isolation of bacteria. Identification of the isolates was performed based on cultural, morphological and biochemical characteristics. The isolates were subjected to antimicrobial susceptibility test (ABST) against the 12 commonly used beta-lactam and non–beta-lactam group of antibiotics by disc diffusion method and further subjected to screening for ESBL double disc diffusion method. Carbapenem-resistant isolates were subjected to phenotypic confirmatory test for carbapenemase production employing Imipenem-EDTA and Ertapenem-boronic acid minimum inhibitory concentration (MIC) strip method.Result: Forty four Gram-negative bacterial isolates obtained were viz., E. coli (30), K. pneumonia (11) and P. aeruginosa (3) from the 100 samples. Apart from these, other isolates obtained were Staphylococcus spp. (53) and Bacillus spp. (2). All the Gram-negative isolates were subjected to ABST employing 12 common antibiotics belonging to beta-lactam and non-beta-lactam groups. Multidrug resistance (MDR) could be observed in 28 E. coli, 11 K. pneumoniae and three P. aeruginosa isolates. All the 42 MDR isolates showed positive results for ESBL production. A total of 14 isolates out of the 44 Gram-negative bacilli were found to be resistant to carbapenem either to imipenem, meropenem or ertapenem. Among the 14 Gram-negative isolates, nine turned out to be positive for metallo-beta-lactamase (MBL) and none for K. penumoniae carbapenemase (KPC) on phenotypic confirmatory test for detecting major carbapenemase enzymes. The present study documented that Gram- negative bacteria like E. coli, K. pneumoniae and P. aeruginosa isolated from dogs are showing an increase rate of resistance against carbapenems which are the last resort drugs against ESBL producers. Hence, there is an urgent need to curb the irrational and excessive use of antibiotics in veterinary sector.


2021 ◽  
Vol 13 (1) ◽  
pp. 77-90
Author(s):  
Ana Kaftandzieva ◽  
Marko Kostovski ◽  
Blerta Mehmeti ◽  
Gordana Mirchevska

Aim: The aim of our study was to determine the most common bacteria isolated from wound samples and tо compare the frequency of the resistant bacteria isolated over a 3-year period. Material and methods: During a three years period (2017-2019) a total of 11 863 wound samples (wound swabs, punctuates, exudates, tissue, etc.) were obtained from the hospitalized patients in the University Clinics of the ,,Mother Theresa” campus, the City hospital ,,8th September” and the University Clinic for surgical diseases ,,St. Naum Ohridski” in Skopje. All samples were processed at the Institute of Microbiology and Parasitology, Faculty of Medicine, Skopje. They were examined by standard microbiology techniques. Identification and susceptibility of microorganisms were done by both standard methods and automatized Vitek 2 system. Results: Out of a total number of samples, which was 3 463 in 2017, 4 127 in 2018 and 4 273 in 2019, positive were 2 068 (60%), 2 302 (55.8%) and 2 387 (55.9%), respectively. From the total of aerobes/facultative anaerobes (2 758, 2 949 and 3 279 in three consecutive years, 2017, 2018 and 2019, respectively), Staphylococcus aureus was the most predominant isolate (19.5%, 16.6%, 16.9%) followed by Enterococcus spp (16%, 16%, 16.7%), Pseudomonas aeruginosa (12%, 13%, 12.7%) and E. coli (10%, 10.4%, 10.7%). Considering anaerobic bacteria, the percentage of Gram positive anaerobes (Peptostreptococcus) has decreased from 33% to 18% out of a total number of anaerobes, unlike Gram negative anaerobes in which the increasing percentage was mostly observed in bacteria of the genus Bacteroides (from 39% to 45%). The percentage of the resistant strains of MRSA, CNS-MR and VRE was almost the same in that period. In Gram-negatives the percentage of ESBL-positive isolates of E. coli and Enterobacter spp. increased consecutively from 2017 to 2019. The increase in the percentage of resistant strains was more noticeable in ESBL-positive isolates of Klebsiella pneumonia between 2017 and 2018, but in 2019 a percentage decrease can be observed. Considering carbapenem-resistant (CR) Enterobacterales, an increase in the resistance was noticeable in K. pneumonia. The increase in the percentage of resistant strains in Enterobacter spp. between 2017 and 2018, as well as the decrease between 2018 and 2019 was statistically significant. The percentage of CR-isolates of Pseudomonas aeruginosa was from 30% to 38% and for Acinetobacter spp. this percentage was from 81% to 85%. Conclusion: The knowledge of the most commonly isolated bacterial pathogens, especially the presence of resistant bacteria, is crucial and should be continuously monitored in order to understand, construct and update effective treatment algorithms and guidelines.


Author(s):  
Hua Zou ◽  
Xiaojiong Jia ◽  
Xiao He ◽  
Yan Su ◽  
Ligang Zhou ◽  
...  

Multidrug-resistant (MDR) pathogens are responsible for a substantial burden of morbidity and mortality from neonatal sepsis; however, data on these sepsis-related pathogens among hospitalized neonates in China are not well characterized. In this study, a total of 240 strains were isolated from four Women and Children’s hospitals in Southwest China between 2014 and 2019. Of these included pathogens, 104 (43.33%) were gram-positive bacteria, 129 (53.75%) were gram-negative bacteria, and 7 (2.92%) were fungi. Escherichia coli (E. coli, 34.01%) and Klebsiella pneumoniae (K. pneumoniae, 15.35%) were the main pathogen of neonate bacteremia. ST167 were the most prevalent STs in E. coli and ST11 in K. pneumoniae. Our study found that E. coli (62.71%) was the predominate pathogen of early-onset sepsis, among which 64.86% were MDR. Late-onset sepsis was mainly caused by K. pneumoniae (28.31%) and E. coli (24.78%), with showing that 78.33% of these pathogens were MDR. Notably, the prevalence of EO/LO pathogens were quite different from Indian and south of China. Moreover, we found that blaCTX-M (42.06%) was most dominant resistant genes with about a third isolates (31.09%) were positive for blaCTX-M-15. All the carbapenem-resistant K. pneumoniae were positive for NDM-1. Moreover, late-onset sepsis and antibiotic exposure were significantly associated with MDR infection. Emerging multi-resistant pathogens of sepsis posts a serious threat to neonatal outcomes and emphasizes an urgent need to control their further spread.


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