Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia

Biagi, Mark; Vialichka, Alesia; Jurkovic, M; Wu, Tzi Yi; Shajee, A; Lee, M; Patel, SR; Mendes, Rodrigo E.; Wenzler, Eric

doi:10.1128/aac.00559-20

Cited by 37 publications

(38 citation statements)

References 39 publications

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“…In SIDERO-CR, 1873 carbapenem–nonsusceptible isolates, including Enterobacterales, MDR A. baumannii , MDR P. aeruginosa , and S. maltophilia were collected globally between 2014 and 2016. In vitro data are also available from other studies assessing cefiderocol against a wide range of clinically important isolates collected globally [ 14 , 28 – 30 ] and from Canada [ 31 ], Germany [ 32 ], Greece [ 33 ], Japan [ 34 , 35 ], Spain [ 36 ], Taiwan [ 37 ], the UK [ 38 ] and the USA [ 17 , 39 – 42 ].…”

Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

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Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Syed

2021

Drugs

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Intravenous cefiderocol (Fetroja ® ; Fetcroja ® ) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of β-lactamases (including metallo-β-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01580-4.

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Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

“…maltophilia [ 17 , 28 , 31 , 33 , 37 , 38 , 40 , 41 ]. In MDR strains of Enterobacterales, P. aeruginosa and S. maltophilia , cefiderocol susceptibility was > 95% [ 33 , 36 , 39 , 40 ].…”

Section: Pharmacodynamic Propertiesmentioning

confidence: 99%

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Syed

2021

Drugs

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“…Apart from cefiderocol, minocycline was the most active agent, with 100% of isolates being susceptible. [49][50][51] Similarly, 100 blood isolates of S. maltophilia revealed MICs of £1 mg/L for cefiderocol and superior susceptibility compared to ceftazidime, ceftazidime/avibactam, and ceftolozane/tazobactam. 27 Cefiderocol also showed superiority compared to aminoglycoside and carbapenem-resistant species with MICs ranging from £0.03 to 0.25 mg/L, with the MIC 90 being 0.25 mg/L.…”

Section: S Maltophiliamentioning

confidence: 99%

Does Cefiderocol Have a Potential Role in Cystic Fibrosis Pulmonary Exacerbation Management?

Gavioli¹,

Guardado²,

Haniff³

et al. 2021

Microbial Drug Resistance

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Cystic fibrosis (CF) is associated with frequent pulmonary exacerbations and the need for novel antibiotics against antimicrobial resistance. Cefiderocol is a newly approved therapeutic option active against a variety of multidrug resistant (MDR) bacteria such as gram-negative species commonly encountered by CF patients. This review describes the potential role of cefiderocol against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Burkholderia cepacia complex. Cefiderocol is a potential therapeutic option for MDR pathogens with minimum inhibitory concentrations (MICs) of £4 mg/L. Due to the lack of in vivo evidence in the CF population, cefiderocol may be utilized in patients in which alternative options are lacking due to MDR organisms or rapid pulmonary decline.

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“…Cefiderocol is a novel, parenteral siderophore cephalosporin which is active against Gram-negative, nonfermenting pathogens, including S. maltophilia , even in the presence of carbapenemases due to its stability against these hydrolyzing enzymes ( 12 ). Cefiderocol has shown potent in vitro activity against a range of carbapenem-susceptible and carbapenem-resistant (CR) Gram-negative bacteria collected from around the world, including S. maltophilia strains resistant to other commonly used antibiotics ( 13 – 16 ). Preclinical studies have already demonstrated that cefiderocol is effective in murine thigh ( 17 ) and rat lung ( 18 ) infection models, and this in vivo efficacy appears to correspond well with its in vitro activity.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Activity and In Vivo Efficacy of Cefiderocol against Stenotrophomonas maltophilia

Nakamura

Oota

Matsumoto

et al. 2021

Antimicrob Agents Chemother

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Cefiderocol is a novel siderophore cephalosporin antibiotic with broad coverage against difficult-to-treat Gram-negative bacteria, including those resistant to carbapenems. Its activity against Stenotrophomonas maltophilia was investigated in vitro against clinical isolates and in lung infection models using strains either resistant (SR202006) or susceptible (SR201934, SR200614) to trimethoprim/sulfamethoxazole. Cefiderocol demonstrated potent in vitro activity against all 217 S. maltophilia clinical isolates tested (MIC50: 0.063 μg/mL, MIC90: 0.25 μg/mL). Cefiderocol also demonstrated low MICs against the trimethoprim/sulfamethoxazole-resistant S. maltophilia strains (i.e. SR202006: MIC=0.125 μg/mL). In a neutropenic mouse lung infection model, cefiderocol (30 mg/kg and 100 mg/kg) demonstrated a significant, dose-dependent reduction in the lung viable bacteria cell count compared with untreated controls in S. maltophilia infection and was the only antibiotic tested to show a similar significant effect in a trimethoprim/sulfamethoxazole-resistant S. maltophilia infection. In immunocompetent rat lung infection models of S. maltophilia, humanized dosing of cefiderocol (2 g every 8 hours) and meropenem (1 g every 8 hours) revealed pharmacokinetic profiles similar to those in human subjects and the humanized cefiderocol dosing significantly reduced the lung viable bacteria cell count compared with baseline controls, which received no intervention. Together, the results from these studies suggest that cefiderocol could provide an effective alternative treatment option for S. maltophilia infections in the lower respiratory tract, particularly strains resistant to empiric antibiotics, such as trimethoprim/sulfamethoxazole or minocycline.

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Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia

Cited by 37 publications

References 39 publications

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Does Cefiderocol Have a Potential Role in Cystic Fibrosis Pulmonary Exacerbation Management?

In Vitro Activity and In Vivo Efficacy of Cefiderocol against Stenotrophomonas maltophilia

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