Philippe Morand | PubMed Health

PubMed2026

Contribution of the Arg-33-His replacement in the histidine kinase CpxA to carbapenem and cefiderocol resistance in Serratia marcescens.

OBJECTIVE: The Serratia marcescens ROT_R clinical isolate, which was resistant to almost all β-lactams, including cefiderocol (4 mg/L), was recovered from a neonate 2 months after the isolation of the S. marcescens ROT_S strain that was susceptible to extended-spectrum cephalosporins (ESCs). In this study, we attempted to decipher the mechanism of resistance displayed by the ROT_R isolate. METHODS: The genomes of ROT_S and ROT_R were sequenced using the Illumina and the Oxford Nanopore Technologies. Long and short reads were assembled together, giving rise to a circularized hybrid genome. RESULTS: Genomic comparison between ROT_S and ROT_R disclosed only one mutation (G98A) in the cpxA gene of ROT_R, which led to the Arg-33-His substitution in the histidine kinase of the two-component system CpxA/CpxR. The cpxA alleles of ROT_S and ROT_R were amplified and cloned, thus giving rise to the pCpxA_WT and pCpxA_R33H recombinant plasmids, respectively, which were subsequently introduced into the S. marcescens HatR recipient strain, which lacks functional CpxA. The S. marcescens HatR (pCpxA_R33H) recombinant clone, which produced the altered CpxA_R33H variant, differed from the S. marcescens HatR (pCpxA_WT) recombinant clone, which produced the wild-type CpxA, by enhanced MICs of carbapenems and ESCs, including cefiderocol (1 mg/L). CONCLUSIONS: This study demonstrates that CpxA alteration, such as Arg-33-His substitution, can contribute to cefiderocol resistance. Although it increases slightly the MIC of cefiderocol without resulting per se in clinical resistance, it can contribute, in combination with other additional mechanisms, to achieve a high level of resistance to this siderophore cephalosporin.

Cefiderocol↗

PubMed2004

[Etiology of bacterial infections in febrile neutropenic patients: the role of the laboratory in the diagnosis].

EPIDEMIOLOGICAL EVOLUTION: Until the mid-eighties, infectious complications (pneumonia, septicemia) observed in neutropenic patients were, in 70% of cases, of bacterial origin with Gram negative bacillae (Escherichia coli, Klebsiella sp, Pseudomonas aeruginosa) isolated 8 times out of 10. Among the Gram positive bacteria, Staphylococcus aureus predominated. The etiological profile of bacterial infections has since evolved with a predominance (60 to 70%) of Gram positive bacteria (coagulase-negative staphylococci, viridans streptococci) and a change in the epidemiology of the Gram positive bacteria notably with a lesser frequency of P. aeruginosa infections. THE GRAM POSITIVE BACTERIA: Coagulase-negative staphylococci are among the first germs responsible for nosocomial bacteremia (central venous catheters) and they are usually multiresistant. Viridans streptococci are a frequent cause of bacteremia; they are generally sensitive to antibiotics active on Gram positive bacteria, but the incidence of resistant strains is increasing. Enterococci are in majority responsible for colonisation in neutropenic patients and less frequently for infections; they raise the problem of resistance to antibiotics, notably to glycopeptides. Other Gram positive bacteria can be responsible for infections in neutropenic patients; it is crucial that they be identified because they require treatment with an appropriate antibiotic. GRAM NEGATIVE BACTERIA: Among the enterobacteria, Escherichia coli is predominantly isolated and raises the problem of the increasing incidence of resistance to fluoroquinolone. Pseudomonas aeruginosa, less frequently responsible today, remains associated with a far greater rate of mortality than that observed with the other microorganisms. Other Gram negative bacteria can be identified; they require an adapted antibiotherapy because they are often naturally multiresistant to antibiotics. THE ROLE OF THE LABORATORY: For the diagnosis of infections in neutropenic patients, the microbiology laboratory has a determinating role. The laboratory ensures the analysis of various biological examinations: blood cultures, methods permitting the diagnosis of an infection on a permanent catheter, copro-cultures (research for common enteropathogens, quantification in the case of digestive decontamination, screening for multiresistant bacteria), cytobacteriological examination of urine, samples of respiratory origin, cytobacteriological examination of cerebro-spinal fluid...).

Bacteremia↗

PubMed2002

Native valve endocarditis due to Enterococcus hirae.

Enterococcus hirae is a rare isolate in clinical specimens. We describe a case of native aortic-valve endocarditis that was caused by Enterococcus hirae in a 72-year-old man. This is the first reported case of endocarditis due to this organism.

Aged↗