In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study)

Kazmierczak, Krystyna M.; Tsuji, Masakatsu; Wise, Mark G.; Hackel, Meredith; Yamano, Yoshinori; Echols, Roger; Sahm, Daniel F.

doi:10.1016/j.ijantimicag.2018.10.007

Cited by 154 publications

(167 citation statements)

References 18 publications

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“…95 As a result of its binding with ferric iron, FDC is actively transported across the outer membrane of GNB, leading to high concentrations in the periplasmic space where it can then bind to PBPs. 96,97 It is also stable to both serine-carbapenemases and MBLcarbapenemases. Data from global surveillance studies for FDC demonstrated potent in vitro activity against a wide spectrum of MDR-GNB, including PSA.…”

Section: Imipenem-cilastatin-relebactam and Cefiderocolmentioning

confidence: 99%

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

2020

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Multidrug resistance(MDR) among Pseudomonas aeruginosa (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR‐PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR‐PSA (e.g., ceftolozane‐tazobactam, ceftazidime‐avibactam, imipenem‐relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR‐PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR‐PSA.

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Section: Imipenem-cilastatin-relebactam and Cefiderocolmentioning

confidence: 99%

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

2020

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“…CMS treatment is particularly recommended when carbapenem resistance is reported. Cefiderocol is another therapeutic agent effective against MDRO like CROs 10 11. However, cefiderocol and similar agents are expensive with limited availability in low-income and middle-income countries (LMICs).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of colistin in multidrug-resistant neonatal sepsis: experience from a tertiary care center in Karachi, Pakistan

Gul

Salat²,

Hussain

et al. 2020

Arch Dis Child

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ObjectiveInfections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates.Design/setting/patients/outcomesWe conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression.Results153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance.ConclusionsColistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.

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“…The resist ance prevalence in CRE and CRPA is a little lower than with ceftazidime-avibactam 64 . The main weakness of cefiderocol is its limited activity against NDM producing E. coli as well as OXA23 producing and OXA24 producing Acinetobacter spp 65 . MIC 90 values are about eight doubling dilutions higher in KPC2 producing Enterobacterales than in wild type strains.…”

Section: New Stand-alone β-Lactam Antibioticsmentioning

confidence: 99%

“…Similarly, the reduced susceptibility of ESBL producing, carbapenemase producing or AmpC producing strains may not translate into immediate clinical resistance 63 but may be problem atic in critically ill patients with altered pharmacokinetic profiles. However, the most problematic XDR or PDR strains have variable susceptibility, with ~64% of NDM producing pathogens testing as susceptible 65 . MICs clustering around the breakpoint may be the beginning of a stepwise development of resistance, and reliable susceptibility testing will be essential.…”

Section: New Stand-alone β-Lactam Antibioticsmentioning

confidence: 99%

Critical analysis of antibacterial agents in clinical development

Theuretzbacher¹,

et al. 2020

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| The antibacterial agents currently in clinical development are predominantly derivatives of well-established antibiotic classes and were selected to address the class-specific resistance mechanisms and determinants that were known at the time of their discovery. Many of these agents aim to target the antibiotic-resistant priority pathogens listed by the WHO, including Gram-negative bacteria in the critical priority category, such as carbapenem-resistant Acinetobacter, Pseudomonas and Enterobacterales. Although some current compounds in the pipeline have exhibited increased susceptibility rates in surveillance studies that depend on geography, pre-existing cross-resistance both within and across antibacterial classes limits the activity of many of the new agents against the most extensively drug-resistant (XDR) and pan-drug-resistant (PDR) Gram-negative pathogens. In particular, cross-resistance to unrelated classes may occur by co-selection of resistant strains, thus leading to the rapid emergence and subsequent spread of resistance. There is a continued need for innovation and new-class antibacterial agents in order to provide effective therapeutic options against infections specifically caused by XDR and PDR Gram-negative bacteria. ✉

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In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study)

Cited by 154 publications

References 18 publications

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

Efficacy of colistin in multidrug-resistant neonatal sepsis: experience from a tertiary care center in Karachi, Pakistan

Critical analysis of antibacterial agents in clinical development

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