Risk factors for acute kidney injury in critically ill patients with bacteraemia by carbapenem non-susceptible Gram negative bacteria.

The objectives of the present study were to identify risk factors for development of acute kidney injury (AKI) during the treatment of bacteraemia due to carbapenem non-susceptible Gram-negative bacteria (CnS-GNB) and its role on mortality. Data of all patients with bacteraemia by CnS-GNB in the intensive care unit of a tertiary hospital from 2012 to 2016 were included. AKI was defined by AKIN criteria. Secondary outcomes were AKI development in patients treated with colistin and predictors of 14-day mortality. Among 285 episodes of bacteraemia due to CnS-GNB, 84 (29.5%) developed AKI. Multivariate analysis revealed that obesity, septic shock, maximum noradrenaline dose and eGFR<60 mL/min/1.73m² upon bacteraemia onset were independently associated with development of AKI. Out of 228 patients receiving colistin, 64 (28.1%) developed AKI. Multivariate analysis found the same factors as before in addition to voriconazole administration. Fourteen-day mortality was 34.2% and was independently associated with bacteraemia by Pseudomonas aeruginosa, AKI during bacteraemia treatment, maximum noradrenaline dose, SAPS II and SOFA scores upon bacteraemia onset, whereas appropriate combination therapy and catheter-related bacteraemia were independently associated with better survival. AKI was a frequent complication of bacteraemia by CnS-GNB and was associated with septic shock and baseline renal function impairment. Mortality was higher among patients that developed AKI due to bacteraemia. Colistin should be considered a safe therapeutic option for treating such infections.

Molecular epidemiology and risk factors for colistin- or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients during a 7-year period.

A matched 1:2 case-control study was conducted among critically ill patients in order to identify the risk factors of colistin or tigecycline-resistant carbapenemase-producing Klebsiella pneumoniae (ColR-Kp, TigR-Kp) bacteraemia. MIC to colistin and tigecycline were determined by Etest. From 224 bacteraemic patients, 46.4% and 29.5% were resistant to colistin and tigecycline, respectively. PCR revealed that 199 isolates carried the blaKPC gene. PCR revealed that no isolate carried the mcr-1 gene. Risk factors for ColR-Kp bacteraemia as compared to patients with bacteraemia by a colistin-susceptible isolate or patients without carbapenemase-producing K. pneumoniae bacteraemia were colistin or tigecycline administration and tracheostomy, while TigR-Kp bacteraemia as compared to either patients with bacteraemia by tigecycline-susceptible isolate or patients without carbapenemase-producing K. pneumoniae bacteraemia were colistin or tigecycline administration, number of comorbidities and prior bacteraemia by a Gram-negative pathogen. Administration of colistin and tigecycline predisposed to development of bacteraemia by either ColR-Kp or TigR-Kp.

Early KPC-Producing Klebsiella pneumoniae Bacteremia among Intensive Care Unit Patients Non-Colonized upon Admission.

Among 140 patients colonized by KPC-producing Klebsiella pneumoniae (KPC-Kp) between fourth and seventh day of Intensive Care Unit stay, 24 developed bacteraemia immediately after colonization. Colistin-resistance of the colonizing isolate was the factor significantly associated with early KPC-Kp bacteraemia (P < 0.001; OR 6.6, 95% CI 2.4-18.4), a worrisome finding since infections by colistin-resistant isolates is associated with increased mortality due to limited remaining therapeutic options.

Performance of four different agar plate methods for rectal swabs, synergy disk tests and metallo-ß-lactamase Etest for clinical isolates in detecting carbapenemase-producing Klebsiella pneumoniae.

The aims of the study were to compare four different agar plate methods in the identification of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) from rectal samples and to assess the role of phenotypic methodologies in the identification of carbapenemase type from clinical K. pneumoniae isolates. Two chromogenic agars (Brilliance CRE and CHROMagar KPC) were compared to MacConkey agar plates with ertapenem (ERT) or imipenem (IMP) disks for the identification of CP-Kp from 912 rectal swabs. CP-Kp was detected in 329 samples by either agar methodology (299 K. pneumoniae carbapenemase positive, 27 Verona integron-encoded metallo-ß-lactamase positive and 3 K. pneumoniae carbapenemase and Verona integron-encodedmetallo-ß-lactamase positive). Sensitivity of Brilliance CRE, CHROMagar KPC and MacConkey agar plus IMP or ERT disk (inhibition zone <25 mm) was 96.8, 99.2, 67.2 and 81.8 %, while specificity was 90.9, 78.2, 98.1 and 97.9 %, respectively. Synergy meropenem-disk tests with EDTA or phenylboronic acid were used in order to detect the carbapenemase type as compared to PCR results (blaVIM, blaKPC and blaNDM) from 2515 isolates with reduced susceptibility to any of the Etest-examined carbapenems (ERT, IMP or meropenem). Metallo-ß-lactamase MP/MPI Etest was applied in 616 isolates. Sensitivity was 98.4, 90.9 and 82.2 % for phenylboronic acid synergy test, EDTA synergy test and metallo-ß-lactamase Etest, respectively, while their specificity was high (>97.5 %). Phenotypic methodologies can provide reliable results for the identification of carbapenemase production among K. pneumoniae isolates. Chromogenic agars can be applied in high-risk patients as part of surveillance and infection control programs.

A ten-year surveillance study of carbapenemase-producing Klebsiella pneumoniae in a tertiary care Greek university hospital: predominance of KPC- over VIM- or NDM-producing isolates.

Resistance patterns and carbapenemase gene presence among Klebsiella pneumoniae isolates from the University General Hospital of Patras, Greece during a ten-year period were analysed under a surveillance programme for multi-drug-resistant bacteria. From 2005 to 2014, K. pneumoniae isolates from clinically significant specimens were identified by the Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the agar disc diffusion method and Etest. The strains were tested for the presence of blaVIM, blaIMP, blaKPC, blaNDM and blaOXA-48 genes by PCR. PFGE of chromosomal Xbal DNA digests was performed. A total of 3449 K. pneumoniae isolates were recovered during the last decade. Among them, 1668 (48 %) were carbapenemase-producing: 1333 (80%) K. pneumoniae carbapenemase (KPC)-, 286 (17%) Verona imipenemase (VIM), 45 (3%) KPC- and VIM-, and four New Delhi metallo-beta-lactamase (NDM)-producing. Their resistance rates to gentamicin, colistin and tigecycline were 41%, 23% and 16%, respectively. VIM-producing K. pneumoniae were isolated in 2005 and since 2008 have been endemic. KPC-producing K. pneumoniae (KPC-Kp) isolates were introduced in 2008 and until now represent the predominant carbapenemase-producing K. pneumoniae in our institution. PFGE of 97 KPC-Kp strains identified three types: A, 84 (87%); B, 11 (11%); and E, two (2%). Eleven co-producing KPC and VIM K. pneumoniae isolates belonged to PFGE B. The four NDM-positives were classified to type F. The number of K. pneumoniae bacteraemias increased during the study period, which may be solely attributed to the increase of carbapenemase-producing isolates. The threat of carbapenemase-producing K. pneumoniae emphasizes the urgent need for implementation of infection control measures and budgetary allocations to infection control.

Risk factors for infection and predictors of mortality among patients with KPC-producing Klebsiella pneumoniae bloodstream infections in the intensive care unit.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections in intensive care units (ICUs) are associated with increased mortality. We aimed to determine risk factors for infection and predictors of 30-day mortality in ICU patients with KPC-Kp bloodstream infections (BSI). METHODS: During a 26-month period, patients (n = 273) who stayed more than 6 days in the ICU of the University Hospital of Patras, Greece, were divided into 2 groups, those who developed KPC-Kp BSI and those who did not. K. pneumoniae was identified by Vitek 2 technology. Antibiotic susceptibility testing was performed by agar disk diffusion method. Minimum inhibitory concentrations were determined by Etest. The presence of the blaKPC gene was confirmed by PCR. Molecular typing was performed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Epidemiological data were collected by patient chart review. RESULTS: Five patients had bacteraemia upon admission, while in 48 (17.6%) the BSI developed after 6 days of hospitalization. Risk factors for KPC-Kp BSI in the latter group were the administration of aminoglycosides, number of invasive catheters inserted after the third day, and tracheostomy. The 30-day mortality was 43.4% (23/53 patients). Multivariate analysis revealed that age, SAPS II score at onset of BSI, resistance to colistin, gentamicin, or tigecycline, and septic shock were independently associated with mortality. Treatment with at least 2 appropriate antibiotics was identified as a predictor of a good prognosis. CONCLUSIONS: Many risk factors are involved in KPC-Kp BSI among ICU patients. The high mortality in patients with KPC-KP BSI in the ICU requires the implementation of appropriate infection control measures.

KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the significance of risk factors for its development and its impact on mortality.

A prospective observational study of 226 intensive care unit (ICU) patients was conducted during a 25-month period. Rectal samples were taken at day 1, 4, and 7 and, afterwards, once weekly. Klebsiella pneumoniae was identified using standard techniques, whereas the presence of bla(KPC) gene was confirmed by PCR. During ICU stay, 72.6% of the patients were colonized with Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-Kp). Male gender, prior bed occupants, and patients in nearby beds colonized with KPC-Kp, tracheotomy, number of invasive catheters inserted, and number of antibiotics administered were the major risk factors for KPC-Kp colonization. ICU mortality (35.4%) was significantly related to Simplified Acute Physiology II score and respiratory insufficiency upon admission, cortisone administration, aminoglycoside administration, confirmed KPC-Kp infection, and severe sepsis or septic shock. The high prevalence of KPC-Kp enteric carriage in ICU patients and the significant mortality associated with KPC-Kp infection dictate the importance of early identification and isolation of such carriers.