Anne Doléans-Jordheim

Gemcitabine is active against clinical multiresistant Staphylococcus aureus strains and is synergistic with gentamicin.

This study provides insight into the antibacterial activity of the cytotoxic nucleoside analogue gemcitabine against clinical multiresistant Staphylococcus aureus strains. Classical methods were used for determination of the minimum inhibitory concentration (MIC) and synergy in vitro, and polymerase chain reaction (PCR) products were sequenced to search for mutations in nucleoside kinase genes in resistant strains. Gemcitabine and its derivative CP-4126 were effective against meticillin-susceptible S. aureus (MSSA), meticillin-resistant S. aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) isolates, with MICs ranging between 0.06 mg/L and 4.22 mg/L. Bactericidal activity was shown in time-kill studies as well as synergy with gentamicin. Mutations in the nucleoside kinase gene SadAK were observed in resistant strains, indicating a role for this enzyme in gemcitabine activity. Nucleoside analogues have antimicrobial activity and these results could be used for further identification and development of new antibiotics.

Septic Arthritis Caused by Noncapsulated Haemophilus influenzae

ABSTRACT Since the introduction of type b Haemophilus influenzae vaccination, noncapsulated H. influenzae has become responsible for most cases of invasive H. influenzae diseases. In our two cases of septic arthritis, we isolated strains with β-lactamase-positive amoxicillin-clavulanate resistance (BLPACR). Thus, the increasing prevalence of BLPACR should be taken into account when empirical therapy is chosen for septic arthritis.

Direct Identification of Staphylococcus aureus and Determination of Methicillin Susceptibility From Positive Blood-Culture Bottles in a Bact/ALERT System Using Binax Now S. aureus and PBP2a Tests

Staphylococcus aureus bacteremia is associated with high mortality and morbidity, requiring prompt and appropriate antimicrobial treatment. Therefore, it is important to detect methicillin-resistant S. aureus (MRSA) rapidly from blood cultures. Two immunochromatographic tests, BinaxNow S. aureus and BinaxNow PBP2a, were directly applied to 79 Bact/Alert bottles that were positive for Gram positive cocci in cluster aggregations. Sensitivity and specificity for the identification of S. aureus and determination of methicillin resistance were 94% and 87%, and 100% and 100%, respectively, with less than 30 min of performance time. These tests are efficient and rapid; these tests are valuable alternatives to more sophisticated and expensive methods used in the diagnosis of MRSA bacteremia.

Strong incidence of Pseudomonas aeruginosa on bacterial rrs and ITS genetic structures of cystic fibrosis sputa

Cystic fibrosis (CF) lungs harbor a complex community of interacting microbes, including pathogens like Pseudomonas aeruginosa. Meta-taxogenomic analysis based on V5-V6 rrs PCR products of 52 P. aeruginosa-positive (Pp) and 52 P. aeruginosa-negative (Pn) pooled DNA extracts from CF sputa suggested positive associations between P. aeruginosa and Stenotrophomonas and Prevotella, but negative ones with Haemophilus, Neisseria and Burkholderia. Internal Transcribed Spacer analyses (RISA) from individual DNA extracts identified three significant genetic structures within the CF cohorts, and indicated an impact of P. aeruginosa. RISA clusters Ip and IIIp contained CF sputa with a P. aeruginosa prevalence above 93%, and of 24.2% in cluster IIp. Clusters Ip and IIIp showed lower RISA genetic diversity and richness than IIp. Highly similar cluster IIp RISA profiles were obtained from two patients harboring isolates of a same P. aeruginosa clone, suggesting convergent evolution in the structure of their microbiota. CF patients of cluster IIp had received significantly less antibiotics than patients of clusters Ip and IIIp but harbored the most resistant P. aeruginosa strains. Patients of cluster IIIp were older than those of Ip. The effects of P. aeruginosa on the RISA structures could not be fully dissociated from the above two confounding factors but several trends in these datasets support the conclusion of a strong incidence of P. aeruginosa on the genetic structure of CF lung microbiota.