Reduced susceptibility mechanism to cefiderocol, a siderophore cephalosporin, among clinical isolates from a global surveillance programme (SIDERO-WT-2014)

Kohira, Naoki; Hackel, Meredith; Ishioka, Yoshino; Kuroiwa, Miho; Sahm, Daniel F.; Sato, Takafumi; Maki, Hideki; Yamano, Yoshinori

doi:10.1016/j.jgar.2020.07.009

Cited by 77 publications

(94 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…75 The percentage of Enterobacterales exhibiting a cefiderocol MIC ≤ 2mg/L (FDA susceptible breakpoint) was 41% (n=61) to 85.7% (n=49) among NDM-positive isolates, 80.9% (n=47) to 91.7% (n=12) among VIM-positive isolates, and 87.5% (n=8) to 93.3% (n=15) among IMP-positive isolates. 76,77 The percentage of Enterobacterales exhibiting a cefiderocol MIC ≤ 4 mg/L (CLSI susceptible breakpoint) was 72.1% (n=61) to 89.8% (n=49) among NDM-positive isolates, 91.7% (n=12) to 95.7% (n=47) among VIMpositive isolates, and 87.5% (n=8) to 100% (n=15) among IMP-positive isolates (Table 3). 76,77 In a multinational surveillance study (SIDERO-WT-2014 study), mechanisms of resistance were categorized for cefiderocol non-susceptible isolates and among 5 NDMproducing Enterobacterales isolates, it was found that elevated MICs were most likely due to a co-production of metallo-and serine-beta-lactamases and not impacted by porin protein truncation or loss.…”

Section: Cefiderocolmentioning

confidence: 99%

“…76,77 The percentage of Enterobacterales exhibiting a cefiderocol MIC ≤ 4 mg/L (CLSI susceptible breakpoint) was 72.1% (n=61) to 89.8% (n=49) among NDM-positive isolates, 91.7% (n=12) to 95.7% (n=47) among VIMpositive isolates, and 87.5% (n=8) to 100% (n=15) among IMP-positive isolates (Table 3). 76,77 In a multinational surveillance study (SIDERO-WT-2014 study), mechanisms of resistance were categorized for cefiderocol non-susceptible isolates and among 5 NDMproducing Enterobacterales isolates, it was found that elevated MICs were most likely due to a co-production of metallo-and serine-beta-lactamases and not impacted by porin protein truncation or loss. 76,78 The PK/PD index of cefiderocol for Enterobacterales was determined to be 73.3% and 64.4% fT>MIC in the thigh and lung murine infection models, respectively, including isolates producing MBLs.…”

Section: Cefiderocolmentioning

confidence: 99%

“…76,77 In a multinational surveillance study (SIDERO-WT-2014 study), mechanisms of resistance were categorized for cefiderocol non-susceptible isolates and among 5 NDMproducing Enterobacterales isolates, it was found that elevated MICs were most likely due to a co-production of metallo-and serine-beta-lactamases and not impacted by porin protein truncation or loss. 76,78 The PK/PD index of cefiderocol for Enterobacterales was determined to be 73.3% and 64.4% fT>MIC in the thigh and lung murine infection models, respectively, including isolates producing MBLs. 79 This target appears attainable for organisms up to MIC 4 mg/L.…”

Section: Cefiderocolmentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic Options for Metallo-β-Lactamase-Producing Enterobacterales

Tan

Kim

Baugh

et al. 2021

IDR

View full text Add to dashboard Cite

The spread of metallo-β-lactamase (MBL)-producing Enterobacterales worldwide without the simultaneous increase in active antibiotics makes these organisms an urgent public health threat. This review summarizes recent advancements in diagnostic and treatment strategies for infections caused by MBL-producing Enterobacterales. Adequate treatment of patients infected with MBL-producing Enterobacterales relies on detection of the β-lactamase in the clinic. There are several molecular platforms that are currently available to identify clinically relevant MBLs as well as other important serine-β-lactamases. Once detected, there are several antibiotics that have historically been used for the treatment of MBL-producing Enterobacterales. Antimicrobials such as aminoglycosides, tetracyclines, fosfomycin, and polymyxins often show promising in vitro activity though clinical data are currently lacking to support their widespread use. Ceftazidime-avibactam combined with aztreonam is promising for treatment of infections caused by MBL-producing Enterobacterales and currently has the most clinical data of any available antibiotic to support its use. While cefiderocol has displayed promising activity against MBL-producing Enterobacterales in vitro and in preliminary clinical studies, further clinical studies will better shed light on its place in treatment. Lastly, there are several promising MBL inhibitors in the pipeline, which may further improve the treatment of MBL-producing Enterobacterales.

show abstract

Section: Cefiderocolmentioning

confidence: 99%

Section: Cefiderocolmentioning

confidence: 99%

Section: Cefiderocolmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Options for Metallo-β-Lactamase-Producing Enterobacterales

Tan

Kim

Baugh

et al. 2021

IDR

View full text Add to dashboard Cite

show abstract

“…Minocycline has also been proposed as an option and has been used against carbapenem-resistant isolates [ 132 ], but its role and activity against CAPT-resistant isolates is unclear, especially considering that its susceptibility breakpoints are unclear [ 133 ] and the lack of modern PK/PD studies and randomized controlled trials [ 134 ]. Finally, cefiderocol is active against most A. baumannii , but cefiderocol-resistant strains have already been reported [ 114 , 135 ]. Ampicillin/sulbactam and trimethoprim/sulfamethoxazole have been used against carbapenem-resistant A. baumannii [ 131 , 136 – 138 ], but their role and activity against CAPT-resistant isolates are less clear.…”

Section: Options For Capt-resistant a Baumanniimentioning

confidence: 99%

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

2020

View full text Add to dashboard Cite

The management of carbapenem-resistant infections is often based on polymyxins, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review, we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, polymyxins and tigecycline (CAPT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CAPT-resistant GNB are scarce and based exclusively on few case reports and small case series, but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review, we consolidate the available literature to inform clinicians dealing with CAPT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CAPT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae , Pseudomonas aeruginosa and Acinetobacter baumannii . Several treatment options are currently available for CAPT-resistant K. pneumonia . Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g., polymyxin- or fosfomycin-based synergistic combinations) may represent a last resort option, but their use against CAPT-resistant GNB requires further study.

show abstract

“…Some of these isolates were NDM-1 metallo-β-lactamase or PER-1 extended-spectrum β-lactamase producers; in such cases, the addition of enzyme inhibitors (eg, dipicolinic acid and/or avibactam) was capable of reducing cefiderocol MIC values, suggesting that production of these β-lactamases may contribute to increased cefiderocol MICs. However, cefiderocol exhibited good activity against several isolates producing these enzymes, 29 suggesting that the presence of additional resistance mechanisms is likely necessary to increase MIC values above the susceptibility breakpoint.…”

Section: Antimicrobial Propertiesmentioning

confidence: 99%