Comparative Study of the Effects of Ceftizoxime, Piperacillin, and Piperacillin-Tazobactam Concentrations on Antibacterial Activity and Selection of Antibiotic-Resistant Mutants of
            <i>Enterobacter cloacae</i>
            and
            <i>Bacteroides fragilis</i>
            In Vitro and In Vivo in Mixed-Infection Abscesses

Stearne, Lorna E. T.; Boxtel, Doret van; Lemmens, Nicole; Goessens, W. H. F.; Mouton, Johan W.; Gyssens, Inge C.

doi:10.1128/aac.48.5.1688-1698.2004

Cited by 23 publications

(20 citation statements)

References 38 publications

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“…Enterobacter strains can be involved in such infections (9,31). We acknowledge that the PDI values reported here were obtained from experiments using a single E. cloacae-cephalosporin combination and that this preferential selection may not be common to all Enterobacter/Enterobacteriaceae strains (25,30). Indeed, none of the dosing regimens increased the frequency with which CZX-resistant strains of B. fragilis were isolated from the abscesses (30).…”

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confidence: 90%

“…Ceftizoxime (CZX) (Cefizox)-resistant mutants of Enterobacter cloacae were selected within 24 h of treatment with lower doses of this cephalosporin but were not found with higher doses of the antibiotic. Since a single dosing frequency (every 2 h [q2h]) was used for these studies, it was not possible to distinguish between the time that the unbound concentrations exceed the MIC (fTϾMIC) and other PDIs describing efficacy and emergence of resistance (30). In the present investigation, we have extended our previous study to include different dosing regimens to determine the PDI important for the emergence of resistant mutants and to establish the PDI value needed for the prevention of this type of resistance.…”

Section: To 10mentioning

confidence: 99%

“…Bacteroides fragilis ATCC 23745 and a clinical isolate, Enterobacter cloacae 22491, were used. The MICs of CZX for these strains were 1 and 0.25 g/ml, respectively (30). Cultures grown overnight were obtained by inoculating 30-ml volumes of WC broth with 0.1 ml of standardized frozen bacterial suspensions (28) and incubating them aerobically (E. cloacae) or anaerobically (B. fragilis) at 37°C for 18 h.…”

Section: To 10mentioning

confidence: 99%

“…Indeed, none of the dosing regimens increased the frequency with which CZX-resistant strains of B. fragilis were isolated from the abscesses (30). Nevertheless, expanded-spectrum cephalosporins are still widely used for empirical treatment (5) and surgical prophylaxis (11), and they are more likely to select resistant strains of Enterobacteriaceae than any other ␤-lactam (26,30). The findings of this study also challenge the practice of administering ␤-lactams in small frequent doses or by continuous infusion (19) as an appropriate procedure for treatment with certain cephalosporins.…”

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confidence: 99%

“…We acknowledge that the PDI values reported here were obtained from experiments using a single E. cloacae-cephalosporin combination and that this preferential selection may not be common to all Enterobacter/Enterobacteriaceae strains (25,30). Indeed, none of the dosing regimens increased the frequency with which CZX-resistant strains of B. fragilis were isolated from the abscesses (30). Nevertheless, expanded-spectrum cephalosporins are still widely used for empirical treatment (5) and surgical prophylaxis (11), and they are more likely to select resistant strains of Enterobacteriaceae than any other ␤-lactam (26,30).…”

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confidence: 99%

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Effect of Dosing and Dosing Frequency on the Efficacy of Ceftizoxime and the Emergence of Ceftizoxime Resistance during the Early Development of Murine Abscesses Caused by Bacteroides fragilis and Enterobacter cloacae Mixed Infection

Stearne¹,

Goessens²,

Mouton

et al. 2007

Antimicrob Agents Chemother

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The efficacy of ␤-lactams is thought to be dependent on the time that the unbound concentrations exceed the MIC (fT>MIC). However, the pharmacokinetic/pharmacodynamic index (PDI) that correlates best to the selection of resistance is not yet clear. The selection of ceftizoxime (CZX)-resistant Enterobacter cloacae mutant strains during the development of murine mixed-infection abscesses was studied to determine the PDI that is important for the emergence of resistance and the PDI value needed for the prevention of resistance. Studies were carried out 24 h after inoculation with Bacteroides fragilis ATCC 23745 and E. cloacae 22491. Six to 1,536 mg of CZX/kg of body weight/day given every 2 h (q2h), q4h, q6h, or q8h was started 30 min before inoculation and continued for 24 h. Resistant mutants were isolated to determine mutant frequencies (MF). The fT>MIC varied from 9 to 98% for E. cloacae, the peak concentration (unbound fraction) was 0.6 to 578 mg/liter, and the area under the concentration-time curve (unbound fraction) (fAUC) was 1.9 to 553 mg ⅐ h/liter. The fAUC-to-MIC ratio best explained the in vivo efficacy. CZX-resistant B. fragilis and E. cloacae mutants were isolated from untreated controls at an MF of 10 ؊5 to 10 ؊7 . The MF of resistant B. fragilis did not increase during therapy. The selection of resistant E. cloacae strains at an MF of 10 ؊1 to 10 ؊2 was related to the fT>MIC and the ratio of fAUC to MIC following an inverse U shape. However, the ratio of fAUC to MIC was the stronger driver of resistance. The highest MFs were 0.7 to 0.9 at an fAUC-to-MIC ratio of approximately 250. We conclude that the ratio of fAUC to MIC is the PDI that correlated best to the in vivo efficacy of CZX and probably also to the emergence of resistant E. cloacae mutants. An fAUC-to-MIC ratio of 1,000 was needed to prevent the emergence of this resistance.The emergence of resistant bacterial strains during ␤-lactam therapy is associated with the intensity of ␤-lactam use (12,20,32) and with prolonged antibiotic exposure (14). Until now, antibiotic dosing regimens used to treat infections have been based primarily on the pharmacokinetic/pharmacodynamic index (PDI) (18) that describes the optimal efficacy and/or prevention of toxicity. However, the increasing problem of emergence of resistance under the influence of antibiotic selection necessitates the need to determine the PDI that correlates best to the development of this resistance.To date, there have been very few studies that have investigated the PDI that is important for the emergence of ␤-lactam resistance. While the ratio of the area under the concentrationtime curve (AUC) at 24 h to MIC of Ն100 (10, 33, 36) or a peak-to-MIC ratio of 8 to 10 (3, 8) may significantly reduce the emergence of resistant subpopulations during treatment with fluoroquinolones and aminoglycosides, it has been reported that these indices do not appear to play an important role in the suppression of resistance during ␤-lactam therapy (33). However, recent findings have indicated the impo...

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confidence: 90%

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confidence: 99%

Section: To 10mentioning

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confidence: 99%

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confidence: 99%

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Effect of Dosing and Dosing Frequency on the Efficacy of Ceftizoxime and the Emergence of Ceftizoxime Resistance during the Early Development of Murine Abscesses Caused by Bacteroides fragilis and Enterobacter cloacae Mixed Infection

Stearne¹,

Goessens²,

Mouton

et al. 2007

Antimicrob Agents Chemother

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Cefiderocol: A Novel Siderophore Cephalosporin against Multidrug‐Resistant Gram‐Negative Pathogens

et al. 2020

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Cefiderocol (CFDC), (formerly S-649266), is a novel injectable siderophore cephalosporin developed by Shionogi & Co., Ltd., with potent in vitro activity against Gram-negative pathogens including multidrug-resistant (MDR) Enterobacteriaceae and non-fermenting organisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cepacia, and Stenotrophomonas maltophilia. Characterized by its siderophore catechol-moiety, CFDC uses a "trojan-horse approach" to navigate through the bacterial periplasmic space, thus evading various beta-lactam degrading enzymes and other mechanisms of resistance present in Gram-negative bacteria. More specifically in carbapenem-resistant Enterobacteriaceae, CFDC has been shown to have activity against extended spectrum beta-lactamases (ESBLs), such as CTX-type, SHV-type, and TEM-type, as well as the Ambler classes of beta-lactamases, including class A (KPC), class B (NDM, IMP, and VIM), class C (AmpC), and class D (OXA, OXA-24, OXA-48, and OXA-48-like). In addition to the strong activity that CFDC has been shown to have against MDR P. aeruginosa, it has also displayed activity against the OXA-23, OXA-24, and OXA-51, beta-lactamases commonly found in MDR A. baumannii. Cefiderocol was recently approved by the US Food and Drug Administration (FDA) for use in complicated urinary tract infections (cUTI), including pyelonephritis, for use in patients 18 years or older with limited or no alternative options for treatment, and is currently being evaluated in a phase III trial for use in nosocomial pneumonia caused by Gram-negative pathogens. The unique features and enhanced activity of CFDC suggest that it is likely to serve as a viable therapeutic option in the treatment of MDR Gram-negative infections. The purpose of this review is to provide an overview of previously published literature explaining CFDC's pharmacology, pharmacokinetic / pharmacodynamic (PK / PD) properties, microbiologic activity, resistance mechanisms, safety parameters, dosing and administration, clinical data, and potential place in therapy. KEY WORDS siderophore, multidrug-resistant Gram-negative pathogens, Acinetobacter baumannii, Pseudomonas aeruginosa, trojan horse, cefiderocol, enterobacterales.

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Risk Factors for Colonization with Third–Generation Cephalosporin–Resistant Enterobacteriaceae

2005

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Comparative Study of the Effects of Ceftizoxime, Piperacillin, and Piperacillin-Tazobactam Concentrations on Antibacterial Activity and Selection of Antibiotic-Resistant Mutants of Enterobacter cloacae and Bacteroides fragilis In Vitro and In Vivo in Mixed-Infection Abscesses

Cited by 23 publications

References 38 publications

Effect of Dosing and Dosing Frequency on the Efficacy of Ceftizoxime and the Emergence of Ceftizoxime Resistance during the Early Development of Murine Abscesses Caused by Bacteroides fragilis and Enterobacter cloacae Mixed Infection

Effect of Dosing and Dosing Frequency on the Efficacy of Ceftizoxime and the Emergence of Ceftizoxime Resistance during the Early Development of Murine Abscesses Caused by Bacteroides fragilis and Enterobacter cloacae Mixed Infection

Cefiderocol: A Novel Siderophore Cephalosporin against Multidrug‐Resistant Gram‐Negative Pathogens

Risk Factors for Colonization with Third–Generation Cephalosporin–Resistant Enterobacteriaceae

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