Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review

Mizrahi, Assaf; Delerue, Thibaud; Morel, H; Monnier, Alban Le; Carbonnelle, Étienne; Pilmis, Benoît; Zahar, Jean‐Ralph

doi:10.1016/j.ijantimicag.2019.10.015

Cited by 42 publications

(24 citation statements)

References 54 publications

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“…In the case of treatment with a combination of β-lactam plus aminoglycoside, only susceptibility to the β-lactam was taken into account because monotherapy with aminoglycosides was considered inadequate. We defined optimization as the use of a fourth-generation cephalosporin such as cefepime instead a third-generation cephalosporin for the treatment of AMP-C producing Enterobacteriales (Enterobacter spp., Serratia marcescens, Citrobacter freundii, or Morganella morganii) [17]. De-optimization was the opposite.…”

Section: Potential Impact On Antibiotic Therapymentioning

confidence: 99%

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

et al. 2020

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Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 h. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study, we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheter (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital: the medical and infectious diseases ICU, the surgical ICU, and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotic changes they would have made if the M-PCR results had been available. Results: We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 h (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95% CI, 73-88%) and specificity of 99% (95% CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p = 0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods.

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Section: Potential Impact On Antibiotic Therapymentioning

confidence: 99%

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

et al. 2020

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“…In addition, to increase the chances of detection of 3GC-R strains in the bacterial population, the same medium supplemented with ceftriaxone at 4 mg/L was also inoculated. Plates were incubated for 16-20 h at 37 • C. This antibiotic was selected as it is considered to be a weak inducer of CoP as other 3GCs (Mizrahi et al, 2020). A maximum of five presumptive ECC colonies from each plate were isolated and identified by matrix-assisted laser desorption/ionization time-offlight mass spectrometry (Shimadzu Biotech, Kyoto, Japan) and associated software.…”

Section: Ecc Isolation and Antibiotic Susceptibility Analysismentioning

confidence: 99%

“…They are intrinsically resistant to aminopenicillin, the combination amoxicillinclavulanic acid, and the first two generations of cephalosporins because they express an inducible ampC cephalosporinase. Under selection pressure, derepressed mutants often emerge, which overproduce cephalosporinase, conferring a high level of resistance to third-generation cephalosporins (3GCs) and increasing the minimum inhibitory concentration required for the fourth generation, such as cefepime (Guérin et al, 2015;Kohlmann et al, 2019;Mizrahi et al, 2020). Since the emergence of extended-spectrum beta-lactamase (ESBL), plasmidic acquisition of ESBL determinants has become an important mechanism in 3GCs resistance (3GC-R), especially among clinical ECC strains, as for most Enterobacteriaceae.…”

Section: Introductionmentioning

confidence: 99%

Wide Distribution and Specific Resistance Pattern to Third-Generation Cephalosporins of Enterobacter cloacae Complex Members in Humans and in the Environment in Guadeloupe (French West Indies)

et al. 2021

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Species belonging to Enterobacter cloacae complex have been isolated in numerous environments and samples of various origins. They are also involved in opportunistic infections in plants, animals, and humans. Previous prospection in Guadeloupe (French West Indies) indicated a high frequency of E. cloacae complex strains resistant to third-generation cephalosporins (3GCs) in a local lizard population (Anolis marmoratus), but knowledge of the distribution and resistance of these strains in humans and the environment is limited. The aim of this study was to compare the distribution and antibiotic susceptibility pattern of E. cloacae complex members from different sources in a “one health” approach and to find possible explanations for the high level of resistance in non-human samples. E. cloacae complex strains were collected between January 2017 and the end of 2018 from anoles, farm animals, local fresh produce, water, and clinical human samples. Isolates were characterized by the heat-shock protein 60 gene-fragment typing method, and whole-genome sequencing was conducted on the most frequent clusters (i.e., C-VI and C-VIII). The prevalence of resistance to 3GCs was relatively high (56/346, 16.2%) in non-human samples. The associated resistance mechanism was related to an AmpC overproduction; however, in human samples, most of the resistant strains (40/62) produced an extended-spectrum beta-lactamase. No relation was found between resistance in isolates from wild anoles (35/168) and human activities. Specific core-genome phylogenetic analysis highlighted an important diversity in this bacterial population and no wide circulation among the different compartments. In our setting, the mutations responsible for resistance to 3GCs, especially in ampD, were diverse and not compartment specific. In conclusion, high levels of resistance in non-human E. cloacae complex isolates are probably due to environmental factors that favor the selection of these resistant strains, and this will be explored further.

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“…We de ned optimization as the use of a fourth-generation cephalosporin such as cefepime instead a third-generation cephalosporin for the treatment of AMP-C producing Enterobacteriales (Enterobacter spp., S. marcescens, C. freundii, or M. morganii). 18 De-optimization was the opposite. The change was considered as inadequate (inadequacy) when Unyvero results led to a switch from an effective antibiotic to an ineffective antibiotic on causative bacteria.…”

Section: Potential Impact On Antibiotic Therapymentioning

confidence: 99%

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

Peiffer-Smadja

Bouadma

Mathy

et al. 2020

Preprint

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Background: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 hours. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods: In this prospective study we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheters (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital; the medical and infectious diseases ICU, the surgical ICU and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotics changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 hours (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95%CI, 73-88%) and specificity of 99% (95%CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p=0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.

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Infections caused by naturally AmpC-producing Enterobacteriaceae: Can we use third-generation cephalosporins? A narrative review

Cited by 42 publications

References 54 publications

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

Wide Distribution and Specific Resistance Pattern to Third-Generation Cephalosporins of Enterobacter cloacae Complex Members in Humans and in the Environment in Guadeloupe (French West Indies)

Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia

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