SUMMARY: Although plasmid-mediated quinolone resistance (PMQR) was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. The best-described form of PMQR is determined by theqnrgroup of genes. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins. These proteins reduce susceptibility to quinolones by protecting the complex of DNA and DNA gyrase or topoisomerase IV enzymes from the inhibitory effect of quinolones. Two additional PMQR mechanisms were recently described.aac(6′)-Ib-crencodes a variant aminoglycoside acetyltransferase with two amino acid alterations allowing it to inactivate ciprofloxacin through the acetylation of its piperazinyl substituent.oqxABandqepAencode efflux pumps that extrude quinolones. All of these genes determine relatively small increases in the MICs of quinolones, but these changes are sufficient to facilitate the selection of mutants with higher levels of resistance. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Several factors suggest their importance in this process, including their increasing ubiquity, their association with other resistance elements, and their emergence simultaneous with the expansion of clinical quinolone resistance. Of concern, these genes are not yet being taken into account in resistance screening by clinical microbiology laboratories.

We characterized distinctive features of a hypertransmissible carbapenem-resistant Klebsiella pneumoniae (CRKP) clone that emerged at Hadassah Hospital, Ein-Kerem, Jerusalem, Israel, in 2006. Eleven CRKP isolated at Hadassah Hospital during 2005–09 were examined by antimicrobial susceptibility testing, PFGE and multilocus sequence typing (MLST). Plasmids were analysed by conjugation, restriction mapping, PCR and sequencing. Divergence from the national epidemic sequence type (ST) ST258 to ST512 was observed early on. Carbapenem resistance was conferred by bla_KPC-3 carried on a plasmid apparently closely related to pKpQIL, also from Israel. This clone also carried a 15 kb plasmid, designated pAAC154, that carries a Tn1331 derivative containing the aac(6′)-Ib gene. pAAC154 does not carry a bla_KPC gene, but is similar to pS15, a plasmid from New York that carries bla_KPC-2. A single CRKP clone ST512 has spread efficiently in our region. In this clone, aac(6′)-Ib, common in CRKP strains, is carried on a different plasmid from bla_KPC-3.

Clinical isolates of Klebsiella pneumoniae and Enterobacter spp. collected from 1990 through 2005 at a tertiary care center were studied for qnr genes. Isolates bearing these genes emerged in the mid-1990s, coinciding with the time of a rapid increase in fluoroquinolone resistance. Sixty percent of these isolates were ciprofloxacin susceptible by CLSI breakpoints.

Tolerance is the ability of bacteria to survive transient exposure to high concentrations of a bactericidal antibiotic without a change in the minimal inhibitory concentration, thereby limiting the efficacy of antimicrobials. The study sought to determine the prevalence of tolerance in a prospective cohort of E. coli bloodstream infection and to explore the association of tolerance with reinfection risk. Tolerance, determined by the Tolerance Disk Test (TDtest), was tested in a prospective cohort of consecutive patient-unique E. coli bloodstream isolates and a collection of strains from patients who had recurrent blood cultures with E. coli (cohorts 1 and 2, respectively). Selected isolates were further analyzed using time-dependent killing and typed using whole-genome sequencing. Covariate data were retrieved from electronic medical records. The association between tolerance and reinfection was assessed by the Cox proportional-hazards regression and a Poisson regression models. In cohort 1, 8/94 isolates (8.5%) were tolerant. Using multivariate analysis, it was determined that the risk for reinfection in the patients with tolerant index bacteremia was significantly higher than for patients with a nontolerant strain, hazard ratio, 3.98 (95% confidence interval, 1.32–12.01). The prevalence of tolerance among cohort 2 was higher than in cohort 1, 6/21(28.6%) vs 8/94 (8.5%), respectively (P = .02). Tolerant E. coli are frequently encountered among bloodstream isolates and are associated with an increased risk of reinfection. The TDtest appears to be a practicable approach for tolerance detection and could improve future patient management.

Plasmodium falciparum, the deadliest form of human malaria, remains one of the major threats to human health in endemic regions. Its virulence is attributed to its ability to modify infected red blood cells (iRBC) to adhere to endothelial receptors by placing variable antigens known as PfEMP1 on the iRBC surface. PfEMP1 expression determines the cytoadhesive properties of the iRBCs and is implicated in severe malaria. To evade antibody‐mediated responses, the parasite undergoes continuous switches of expression between different PfEMP1 variants. Recently, it became clear that in addition to antibody‐mediated responses, PfEMP1 triggers innate immune responses; however, the role of neutrophils, the most abundant white blood cells in the human circulation, in malaria remains elusive. Here, we show that neutrophils recognize and kill blood‐stage P. falciparum isolates. We identify neutrophil ICAM‐1 and specific PfEMP1 implicated in cerebral malaria as the key molecules involved in this killing. Our data provide mechanistic insight into the interactions between neutrophils and iRBCs and demonstrate the important influence of PfEMP1 on the selective innate response to cerebral malaria.