Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'. In the last two decades, numerous high-risk (HiR) MDR and XDR K. pneumoniae sequence types have emerged showing superior ability to cause multicontinent outbreaks, and continuous global dissemination. The data highlight the complex evolution of MDR and XDR K. pneumoniae, involving transfer and spread of ARGs, and epidemic plasmids in highly disseminating successful clones. With the worldwide catastrophe of antibiotic resistance and the urgent need to identify the main pathogens that pose a threat on the future of infectious diseases, further studies are warranted to determine the epidemic traits and plasmid acquisition in K. pneumoniae. There is a need for future genomic and translational studies to decipher specific targets in HiR clones to design targeted prevention and treatment.

Pseudomonas aeruginosa, a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR P. aeruginosa and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR P. aeruginosa, and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR P. aeruginosa. Having a malignant disease was a protective factor (odds ratio [OR] ‫؍‬ 0.2; P ‫؍‬ 0.03). MDR P. aeruginosa was associated with severe outcomes compared to controls, including increased mortality (OR ‫؍‬ 4.4; P ‫؍‬ 0.04), hospital stay (hazard ratio, 2; P ‫؍‬ 0.001), and requirement for procedures (OR ‫؍‬ 5.4; P ‫؍‬ 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR P. aeruginosa is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR P. aeruginosa infections are associated with severe adverse clinical outcomes.Pseudomonas aeruginosa is a leading cause of nosocomial infections and is responsible for 10% of all hospital-acquired infections (17, 18). Infections caused by P. aeruginosa are often severe and life threatening and are difficult to treat because of the limited susceptibility to antimicrobial agents and the high frequency of an emergence of antibiotic resistance during therapy (3, 9), thus resulting in severe adverse outcomes (4).The problem of antibiotic resistance in P. aeruginosa is on the increase (18). The heightened level of drug resistance is a result of the de novo emergence of resistance in a specific organism after exposure to antimicrobials (3) as well as of patient-to-patient spread of resistant organisms (8). Accumulation of resistance after exposure to various antibiotics and cross-resistance between agents may result in multidrug-resistant (MDR) P. aeruginosa. This condition was found primarily in patients with cystic fibrosis, where persistent infection with P. aeruginosa leads to the sequential emergence of resistance to multiple antibiotic agents. These MDR P. aeruginosa strains may be transmitted from patient to patient and sometimes lead to outbreaks among cystic fibrosis patients attending...

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging nosocomial pathogen. Little is known about its risk factors or mortality. We performed a case-case-control study to assess the risks for CRKP isolation and a retrospective cohort study to assess mortality in three groups of hospitalized adults: (i) patients from whom CRKP was isolated, (ii) patients from whom carbapenem-susceptible Klebsiella spp. (CSKS) were isolated, and (iii) controls from whom no Klebsiella spp. were isolated. After adjustment for length of stay (LOS), the demographics, comorbidities, and exposures of each case group were compared with those of the controls. Significant covariates were incorporated into LOS-adjusted multivariable models. In the mortality study, we evaluated the effect of CRKP on in-hospital death. There were 48 patients with CRKP isolation ( After adjustment for the severity of illness, CRKP isolation remained predictive of death, albeit with a lower OR (for the CRKP group versus the CSKS group, OR, 3.9; 95% CI, 1.1 to 13.6; and P ‫؍‬ 0.03; for the CRKP group versus the controls, OR, 5.0; 95% CI, 1.7 to 14.8; and P ‫؍‬ 0.004). CRKP affects patients with poor functional status, an ICU stay, and antibiotic exposure and is an independent predictor of death.

Klebsiella pneumoniae carbapenemase (KPC)-producing

We describe peptidomimetic oligomers that show rapid, nonhemolytic, broad-spectrum bactericidal properties in mice and do not induce the emergence of resistance. The oligomers contain acyl chains, which prevent the formation of stable secondary structure. This design appears advantageous over conventional antimicrobial peptides with respect to in vivo efficacy and safety, and may provide a convenient platform for the development of peptide antibiotics.

We studied outcomes of extended-spectrum ␤-lactamase (ESBL) production in Enterobacteriaceae bacteremia. Inpatients with bacteremia caused by ESBL-producing Escherichia coli, Klebsiella spp., or Proteus spp. (cases) were compared with patients with bacteremia caused by non-ESBL producers (controls). Outcomes included mortality, mortality due to infection, length of stay (LOS), delay in appropriate therapy (DAT), discharge to a chronic care facility, and hospital cost. Ninety-nine cases and 99 controls were enrolled. Thirty-five percent of cases died, versus 18% of controls (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3 to 4.7; P ‫؍‬ 0.01). Thirty percent of cases died due to infection, versus 16% of controls (OR, 2.3; 95% CI, 1.1 to 4.5; P ‫؍‬ 0.03). The median LOS after bacteremia for cases was 11 days (interquartile range, 5 to 21), versus 5 days for controls (interquartile range, 3 to 9) (P < 0.001). DAT occurred in 66% of cases, versus 7% of controls (OR, 25.1; 95% CI, 10.5 to 60.2; P < 0.001). Cases were more likely than controls to be discharged to chronic care (52% versus 21%; OR, 4.0; 95% CI, 1.9 to 8.3; P < 0.001). The average hospital cost for cases was 65,509 Israeli shekels, versus 23,538 shekels for controls (P < 0.001). After adjusting for differences between groups by using multivariable analysis, ESBL production remained a significant predictor of mortality (OR, 3.6; 95% CI, 1.4 to 9.5; P ‫؍‬ 0.008), increased LOS (1.56-fold; P ‫؍‬ 0.001), DAT (OR, 25.1; 95% CI, 10.5 to 60.2; P < 0.001), and increased cost (1.57-fold; P ‫؍‬ 0.003). The mean increase in equivalent cost attributable to ESBL production was $9,620. ESBL production was associated with severe adverse outcomes, including higher overall and infection-related mortality, increased LOS, DAT, discharge to chronic care, and higher costs.

TOC summary: Clones harboring different plasmids with identical genetic structure could be the origin of worldwide spread.

We report high rates of bacteremia and colonization with ESBL-producing Enterobacteriaceae at admission to our institution, which may undermine infection-control measures and complicate the selection of empirical treatment.