Quiz Ref ID Gram-negative bacteria that produce extended-spectrum β-lactamase (ESBL) enzymes are a global public health concern.¹ Based on national surveillance data from 2011, the US Centers for Disease Control and Prevention estimated that ESBL producers accounted for at least 26 000 infections and 1700 deaths annually.² A key feature of ESBL-producing Enterobacteriaceae is phenotypic resistance to oxyiminocephalosporins, in addition to penicillins.³ ESBL producers are increasingly commonplace in both community and health care settings.⁴ Carbapenems have been regarded as the treatment of choice for serious infections caused by ESBL producers.^3,5 However, increased use of carbapenems may select for carbapenem resistance in gram-negative bacilli,^6,7 which currently represents the greatest threat in terms of antibiotic resistance.

Eighteen carbapenem-resistant, OXA-48-positive enterobacterial isolates recovered from Turkey, Lebanon, Egypt, France, and Belgium were analyzed. In most isolates, similar 70-kb plasmids carrying the carbapenemase gene bla _OXA-48 were identified. That gene was located within either transposon Tn 1999 or transposon Tn 1999.2 , which was always inserted within the same gene. This work highlights the current plasmid-mediated dissemination of the OXA-48 carbapenemase worldwide.

A series of colistin-resistant Klebsiella pneumoniae isolates recovered from different countries was investigated in order to evaluate the involvement of the PmrA/PmrB two-component system in this resistance. Six isolates possessed a mutated PmrB protein, which is encoded by the pmrB gene, part of the pmrCAB operon involved in lipopolysaccharide modification. The same amino acid substitution (Thr157Pro) in PmrB was identified in the six isolates. The six isolates belonged to four distinct clonal groups, recovered in South Africa (sequence type 14 [ST14]), Turkey (ST101), and Colombia (ST258 and ST15). Three out of the four clones produced a carbapenemase, OXA-181, OXA-48, or KPC-3, while a single isolate did not produce any carbapenemase. Expression assays revealed an overexpression of the pmrA (70-fold), pmrB (70-fold), pmrC (170-fold), and pmrK (40-fold) genes in the pmrB -mutated isolate compared to expression of the pmrB wild-type isogenic K. pneumoniae isolate, confirming that the PmrB substitution was responsible for increased expression levels of those genes. Complementation assays leading to the expression of a wild-type PmrB protein restored the susceptibility to colistin in all isolates, confirming that the substitution in PmrB was responsible for the resistance phenotype. This study identified a key amino acid located in the PmrB protein as being responsible for the overexpression of pmrCAB and pmrHFIJKLM operons, leading to resistance to colistin.

Staphylococcus aureus is one of the causes of both community and healthcare-associated bacteremia. The attributable mortality of S. aureus bacteremia (SAB) is still higher and predictors for mortality and clinical outcomes of this condition are need to be clarified. In this prospective observational study, we aimed to examine the predictive factors for mortality in patients with SAB in eight Turkish tertiary care hospitals. Adult patients with signs and symptoms of bacteremia with positive blood cultures for S. aureus were included. All data for episodes of SAB including demographics, clinical and laboratory findings, antibiotics, and outcome were recorded for a 3-year (2010–2012) period. Cox proportional hazard model with forward selection was used to assess the independent effect of risk factors on mortality. A 28-day mortality was the dependent variable in the Cox regression analysis. A total of 255 episodes of SAB were enrolled. The median age of the patients was 59 years. Fifty-five percent of the episodes were considered as primary SAB and vascular catheter was the source of 42.1 %. Healthcare associated SAB was defined in 55.7 %. Blood cultures yielded methicillin-resistant S. aureus (MRSA) as a cause of SAB in 39.2 %. Initial empirical therapy was inappropriate in 28.2 %. Although overall mortality was observed in 52 (20.4 %), 28-day mortality rate was 15.3 %. Both the numbers of initial inappropriate empirical antibiotic treatment and the median hours to start an appropriate antibiotic between the cases of fatal outcome and survivors after fever onset were found to be similar (12/39 vs 60/216 and 6 vs 12 h, respectively; p > 0.05). High Charlson comorbidity index (CCI) score (p = 0.002), MRSA (p = 0.017), intensive care unit (ICU) admission (p < 0.001) and prior exposure to antibiotics (p = 0.002) all were significantly associated with mortality. The Cox analysis defined age [Hazard Ratio (HR) 1.03; p = 0.023], ICU admission (HR 6.9; p = 0.002), and high CCI score (HR 1.32; p = 0.002) as the independent predictive factors mortality. The results of this prospective study showed that age, ICU stay and high CCI score of a patient were the independent predictors of mortality and MRSA was also significantly associated with mortality in SAB.

Twenty-two consecutive carbapenem-resistant enterobacterial isolates were recovered from patients hospitalized between January and April 2013 in different units at a university hospital in Istanbul, Turkey. These were Klebsiella pneumoniae isolates producing the carbapenemases OXA-48, NDM-1, and KPC-2, Enterobacter cloacae isolates producing NDM-1, and Escherichia coli isolates producing OXA-48. Most of the OXA-48-producing K. pneumoniae and all the NDM-1-producing E. cloacae were clonally related. The NDM-1-producing E. cloacae isolates recovered from a single neonatal intensive care unit corresponded to a single cluster, highlighting the spread of that clone in that setting.