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.

Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become more common in the United States and throughout the world. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to examine the molecular epidemiology of KPC-producing K. pneumoniae isolates sent to the Centers for Disease Control and Prevention (CDC) for reference testing from 1996 to 2008. A dominant strain, sequence type 258 (ST 258), was found and likely accounts for 70% of the CDC's K. pneumoniae PFGE database. Isolates with PFGE patterns related to ST 258 were identified in 10 of the 19 U.S. states currently reporting KPC-producing K. pneumoniae , in addition to one isolate from Israel. KPC subtyping and analysis of the surrounding genetic environment were subsequently performed on 23 representative isolates. Thirteen isolates identified as ST 258 possessed either bla _KPC-2 or bla _KPC-3 and some variability in the Tn 4401 element upstream of the bla _KPC gene. Escherichia coli DH10B was successfully transformed by electroporation with KPC-encoding plasmid DNA from 20 of the 23 isolates. Restriction analysis of plasmid DNA prepared from transformants revealed a diversity of band patterns, suggesting the presence of different plasmids harboring the bla _KPC gene, even among isolates of the same ST.

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 (21 died [44%]), 56 patients with CSKS isolation (7 died [12.5%]), and 59 controls (1 died [2%]). Independent risk factors for CRKP isolation were poor functional status (odds ratio [OR], 15.4; 95% confidence interval [CI], 4.0 to 58.6; P < 0.001); intensive care unit (ICU) stay (OR, 17.4; 95% CI, 1.5 to 201.9; P = 0.02); and receipt of antibiotics (OR, 4.4; 95% CI, 1.0 to 19.2; P = 0.05), particularly fluoroquinolones (OR, 7.2; 95% CI, 1.1 to 49.4; P = 0.04). CRKP was independently associated with death when patients with CRKP were compared with patients with CSKS (OR, 5.4; 95% CI, 1.7 to 17.1; P = 0.005) and with controls (OR, 6.7; 95% CI, 2.4 to 18.8; P < 0.001). 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.

We studied outcomes of extended-spectrum β-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.

Klebsiella pneumoniae isolates that produce carbapenemases (KPCs) are rapidly disseminating worldwide. To determine their genetic background, we investigated 16 blaKPC-2-harboring K. pneumoniae isolates from 5 countries. The isolates were multidrug resistant, possessed the blaKPC-2 gene, and differed by additional β-lactamase content. They harbored a naturally chromosome-encoded bla gene (blaSHV-1 [12.5%], blaSHV-11 [68.7%], or blaOKP-A/B [18.8%]) and several acquired and plasmid-encoded genes (blaTEM-1 [81.3%], blaCTX-M-2 [31.3%], blaCTX-M-12 [12.5%], blaCTX-M-15 [18.7%], and blaOXA-9 [37.5%]). The blaKPC-2 gene was always associated with 1 of the Tn4401 isoforms (a, b, or c). Tn4401 was inserted on different-sized plasmids that belonged to different incompatibility groups. Several blaKPC-containing K. pneumoniae clones were found: 9 different pulsotypes with 1 major (sequence type 258) and 7 minor distinct allelic profiles. Different clones harboring different plasmids but having identical genetic structure, Tn4401, could be at the origin of the worldwide spread of this emerging resistance gene.