scholarly journals Current Concepts in Antimicrobial Therapy Against Resistant Gram-Negative Organisms: Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae, Carbapenem-Resistant Enterobacteriaceae, and Multidrug-Resistant Pseudomonas aeruginosa

2011 ◽  
Vol 86 (3) ◽  
pp. 250-259 ◽  
Author(s):  
Souha S. Kanj ◽  
Zeina A. Kanafani
2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Kenneth V. I. Rolston ◽  
Baghat Gerges ◽  
Samuel Shelburne ◽  
Samuel L. Aitken ◽  
Issam Raad ◽  
...  

ABSTRACT Cefiderocol inhibited 97.5% of 478 Gram-negative isolates from cancer patients at ≤4 mg/liter. It had potent activity against extended-spectrum β-lactamase-positive Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE), and nonfermenting Gram-negative bacilli, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter species isolates. Amikacin, ceftazidime-avibactam, and meropenem had appreciable activity against non-CRE Enterobacteriaceae. No comparators were active against multidrug-resistant P. aeruginosa isolates. Only trimethoprim-sulfamethoxazole had appreciable activity against S. maltophilia isolates. Overall, cefiderocol was associated with the lowest level of resistance.


Author(s):  
Miao Wan ◽  
Xun Gao ◽  
Luchao Lv ◽  
Zhongpeng Cai ◽  
Jian-Hua Liu

Tigecycline and colistin are considered 20 as the final options for the treatment of infections caused by multidrug-resistant (MDR) gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (1).…


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S413-S414 ◽  
Author(s):  
Michael R Jacobs ◽  
Ayman M Abdelhamed ◽  
Caryn E Good ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  

Abstract Background Cefiderocol is a novel siderophore cephalosporin targeted for activity against carbapenem and multidrug-resistant Gram-negative species, including extended-spectrum β-lactamase (ESBL) and carbapenemase-producing strains. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multi-center consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of cefiderocol and meropenem were determined by broth microdilution according to current CLSI guidelines. Cefiderocol was tested in iron-depleted cation-adjusted Mueller–Hinton (MH) broth, meropenem was tested in cation-adjusted MH broth. Cefiderocol MICs were read as the first drug well in which the growth was significantly reduced (i.e., a button of <1 mm or light/faint turbidity) relative to the growth observed in the growth control well containing the same medium. Trailing endpoints were disregarded. Isolates tested included 35 Escherichia coli, five Enterobacter/Citrobacter group, and 794 Klebsiella pneumoniae. Isolates had characterized β-lactamases including TEM, SHV, and CTX-M ESBLs and KPC, NDM, and OXA carbapenemases. Results Cefiderocol MICs ranged from ≤0.03 to >64 mg/L, with overall MIC50 of 0.5 mg/L and MIC90 of 4 mg/L (table). MIC90 value (≤0.03 mg/L) was lowest against isolates with no ESBLs or carbapenemases. MIC90 was 1 mg/L for OXA and TEM/SHV groups, 2–4 mg/L for KPC-3 groups and 8 mg/L for NDM and KPC-2 groups. Conclusion Compared with isolates without ESBLs and carbapenemases, cefiderocol shows higher MICs against isolates with ESBLs, including TEM, SHV, and CTX-M and carbapenemases including KPC, NDM, and OXA. The clinical utility of cefiderocol against ESBL and carbapenemase-producing Enterobacteriaceae is dependent on the pharmacokinetic and pharmacodynamic properties of cefiderocol. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, Shionogi: Scientific Advisor, Consulting fee. achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Consultant, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee.


2013 ◽  
Vol 57 (6) ◽  
pp. 2849-2857 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
M. R. K. Alley ◽  
Helio S. Sader ◽  
Douglas J. Biedenbach ◽  
Ronald N. Jones

ABSTRACTAN3365 (MIC50/90, 0.5/1 μg/ml) was active againstEnterobacteriaceae, including a subset ofKlebsiella pneumoniaecarbapenemase (KPC)-producingK. pneumoniaestrains (MIC50/90, 1/2 μg/ml). AN3365 inhibited 98.0 and 92.2% of wild-type (MIC50/90, 2/8 μg/ml) and carbapenem-resistant (MIC50/90, 4/8 μg/ml)Pseudomonas aeruginosastrains, respectively, at ≤8 μg/ml. AN3365 also demonstrated activity against wild-typeAcinetobacter baumannii(MIC50/90, 2/8 μg/ml) andStenotrophomonas maltophilia(MIC50/90, 2/4 μg/ml), while it was less active against multidrug-resistantA. baumannii(MIC50/90, 8/16 μg/ml) andBurkholderia cepacia(MIC50/90, 8/32 μg/ml).


2010 ◽  
Vol 2 (01) ◽  
pp. 014-016 ◽  
Author(s):  
Madhu Sharma ◽  
Sarita Yadav ◽  
Uma Chaudhary

ABSTRACTGram-negative bacilli are important agents causing neonatal sepsis. The organisms isolated are often resistant to multiple antimicrobials specially which are metallo-beta-lactamases (MβL) producers. Therefore, the present study was conducted with the objective to examine the incidence of MβL producing strains in multidrug resistant (MDR) Pseudomonas aeruginosa from cases of neonatal sepsis. Between January-December 2006, 1994 cases of neonatal sepsis were investigated. The isolates obtained were identified and tested for susceptibility to various antimicrobial agents. The multidrug resistant P. aeruginosa isolates were screened for the presence of MβL by imipenem-EDTA disc method. Five hundred and ninety three (29.73%) isolates were obtained from culture of neonates. Most frequent offender was P. aeruginosa (48.2%). There was an overall predominance of gram-negative organisms. MβL production was seen in 69.5% of imipenem-resistant P. aeruginosa isolates. MβL producing P. aeruginosa is an emerging threat in neonatal septicemia and a cause of concern for physicians treating such infections.


2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Michael R. Jacobs ◽  
Ayman M. Abdelhamed ◽  
Caryn E. Good ◽  
Daniel D. Rhoads ◽  
Kristine M. Hujer ◽  
...  

ABSTRACT The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.


2009 ◽  
Vol 53 (10) ◽  
pp. 4352-4356 ◽  
Author(s):  
Jared L. Crandon ◽  
Catharine C. Bulik ◽  
David P. Nicolau

ABSTRACT Doripenem is a new carbapenem antimicrobial with activity against a range of gram-negative organisms, including Pseudomonas aeruginosa. Previous animal studies have shown efficacy of a 500-mg dose of doripenem given as a 4-h infusion against P. aeruginosa with MICs of ≤4 μg/ml. The purpose of this study is to evaluate the efficacy of 1- and 2-g-dose prolonged infusions of doripenem against a wide range of P. aeruginosa isolates in the neutropenic murine thigh model. Eighteen clinical P. aeruginosa isolates (MIC range, 2 to 32 μg/ml) were used; 15 of these were multidrug resistant. After infection, groups of mice were administered doripenem doses designed to simulate the free time above the MIC (fT>MIC) observed in humans given 1 or 2 g of doripenem every 8 h as a 4-h infusion. Efficacy correlated well with published fT>MIC bactericidal targets of 40%. After 24 h, 1- and 2-g doses achieved approximately ≥2 log decreases in CFU against isolates with MICs of ≤8 and 16 μg/ml, respectively (fT>MIC range, 52.5 to 95%). Results with organisms with higher MICs, where fT>MIC was 0%, were variable, including both increases and decreases in CFU. Compared with 1-g doses, statistically greater efficacy was noted for 2-g doses against three of the eight isolates with MICs of ≥16 μg/ml. While MIC distributions of P. aeruginosa at present necessitate increased exposures for only the most-resistant isolates, the ability of increased doses to achieve pharmacodynamic targets and the efficacy observed when these targets were attained could prove useful when these resistant isolates are encountered.


2020 ◽  
Vol 15 (2) ◽  
pp. 92-107
Author(s):  
G. A. Klyasova

Infections are a common complication in patients with hematological malignancies, especially during neutropenia. Recently, an increase in multidrug-resistant gram-negative pathogens has been observed in the etiology of infectious complications, including carbapenem-resistant Enterobacteriaceae. However, therapeutic options for treatment of these infections are limited. The review represents treatment options for infections caused by carbapenem-resistant Enterobacteriaceae, including the use of reserve drugs such as polymyxin, carbapenems, tigecycline, as well as a new antibiotic – ceftazidime-avibactam, which contains a new β-lactamase inhibitor with unique properties.


Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Milo Gatti ◽  
Bruno Viaggi ◽  
Gian Maria Rossolini ◽  
Federico Pea ◽  
Pierluigi Viale

(1) Background: To develop evidence-based algorithms for targeted antibiotic therapy of infection-related ventilator-associated complications (IVACs) caused by non-fermenting Gram-negative pathogens. (2) Methods: A multidisciplinary team of four experts had several rounds of assessments for developing algorithms devoted to targeted antimicrobial therapy of IVACs caused by two non-fermenting Gram-negative pathogens. A literature search was performed on PubMed-MEDLINE (until September 2021) to provide evidence for supporting therapeutic choices. Quality and strength of evidence was established according to a hierarchical scale of the study design. Six different algorithms with associated recommendations in terms of therapeutic choice and dosing optimization were suggested according to the susceptibility pattern of two non-fermenting Gram-negative pathogens: multi-susceptible Pseudomonas aeruginosa (PA), multidrug-resistant (MDR) metallo-beta-lactamase (MBL)-negative-PA, MBL-positive-PA, carbapenem-susceptible Acinetobacter baumannii (AB), and carbapenem-resistant AB. (3) Results: Piperacillin–tazobactam or fourth-generation cephalosporins represent the first therapeutic choice in IVACs caused by multi-susceptible PA. A carbapenem-sparing approach favouring the administration of novel beta-lactam/beta-lactamase inhibitors should be pursued in the management of MDR-MBL-negative PA infections. Cefiderocol should be used as first-line therapy for the management of IVACs caused by MBL-producing-PA or carbapenem-resistant AB. Fosfomycin-based combination therapy, as well as inhaled colistin, could be considered as a reasonable alternative for the management of IVACs due to MDR-PA and carbapenem-resistant AB. (4) Conclusions: The implementation of algorithms focused on prompt revision of antibiotic regimens guided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens is strongly suggested.


2020 ◽  
Vol 3 (4) ◽  
pp. 295-301
Author(s):  
L.G. Boronina ◽  
◽  
E.V. Samatova ◽  
S.M. Blinova ◽  
M.P. Kukushkina ◽  
...  

Aim: to define the incidence of carbapenem-resistant Enterobacteriaceae in the bioassay of hospitalized children. Patients and Methods: From January to December 2019, 940 strains of gram-negative bacteria were isolated from clinical material of 900 patients. Antibiotic susceptibility testing was conducted using the disk diffusion method; SENSITITRE and Phoenix M50 analyzers used «CHROMagarTM KPC» medium. Also, Carbapenem Inactivation Method was used to detect the carbapenemase activity. Results: the species composition of carbapenem-resistant Enterobacteriaceae included: Pseudomonas aeruginosa (n=55), Acinnetobacter baumannii (n=22), Escherichia coli (n=2), Klebsiella pneumoniae (n=40), Klebsiella oxytoca (n=1), Enterobacter cloacae (n=7), Serratia marcescens (n=2), Proteus mirabilis (n=2), Pseudomonas putida (n=1). 12.1% of all Enterobacterales isolates and 29.4% Klebsiella pneumoniae strains were resistant to ertapenem; 17.2% of Enterobacteriaceae and 20% of K. pneumoniae strains were resistant to imipenem and meropenem. 50.9% of Pseudomonas aeruginosa strains were resistant to meropenem and imipenem, and 45% — to doripenem. Acinetobacter baumannii strains resistant to meropenem — 66.6%, imipenem — 63.6%, doripenem — 83.3%. In 30.4% of P. aeruginosa and A. baumannii strains, carbapenemase activity was not detected, which indicated other mechanisms of resistance to carbapenem. Conclusion: in most cases, phenotypic methods only allow to suspect the presence of certain mechanisms of acquired resistance. However, since the main, most common mechanism is the production of hydrolytic enzymes, the identification of mechanisms of resistance to carbapenems should be precisely directed at this. At present, in addition to phenotypic methods, it is optimal to use molecular methods, in particular, realtime PCR, to effectively monitor the distribution of carbapenemase producers. KEYWORDS: Enterobacterales, non-fermenting gram-negative bacteria, carbapenemases, children, infection. FOR CITATION: Boronina L.G., Samatova E.V., Blinova S.M. et al. Incidence of carbapenem-resistant Enterobacteriaceae in the multidisciplinary pediatric hospital. Russian Journal of Woman and Child Health. 2020;3(4):295–301. DOI: 10.32364/2618-8430-2020-3-4-295-301.


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