Sophia Vamvakopoulou

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.

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

Abstract 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.

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.

Eleven-year retrospective survey of candidaemia in a university hospital in southwestern Greece

The aim of this study was to investigate the isolation and distribution rate of Candida spp. in blood cultures and evaluate antifungal susceptibility during an 11-year period (1998–2008) at a tertiary-care hospital. The causative species were as follows: Candida albicans, 163 strains (64%); Candida parapsilosis, 35 strains (13.7%); Candida glabrata, 25 strains (9.8%); Candida tropicalis, 19 strains (7.4%); and other Candida spp., 13 strains (5.1%). Candidaemia is predominantly caused by C. albicans. C. parapsilosis is the most common non-albicans Candida isolated in neonatal intensive-care units. All Candida isolates remain susceptible to amphotericin B, whereas the highest degree of resistance was observed for azoles.

Carbapenemase-producing Klebsiella pneumoniae bloodstream infection in critically ill patients: risk factors and predictors of mortality

A significant increase in carbapenemase-producing Klebsiella pneumoniae (CP-Kp) bacteraemias has been observed worldwide. The objective of the present work was to study the risk factors and predictors of mortality of CP-Kp bacteraemias among critically ill patients. During a 4-year period (2012–3015), a matched 1:2 case-control study was conducted. Klebsiella pneumoniae was identified by Vitek 2 technology. Antibiotic susceptibility was performed by the agar disc diffusion method and Etest. The presence of the blaKPC, blaVIM and blaNDM genes was confirmed by polymerase chain reaction (PCR). Epidemiologic data were collected from the intensive care unit (ICU) computerised database. One hundred and thirty-nine patients who developed a CP-Kp bacteraemia were matched with 278 patients. The majority of isolates (128; 92.1%) carried the blaKPC gene, seven carried both blaKPC and blaVIM, three blaVIM and one carried blaNDM. Risk factors for the development of CP-Kp bacteraemia were administration of tigecycline and number of antibiotics administered prior to CP-Kp bacteraemia. Overall, the 30-day mortality was 36.0%. Multivariate analysis revealed septic shock, Simplified Acute Physiology Score II (SAPS II) upon infection onset, adjunctive corticosteroid administration and parenteral nutrition as independent predictors of mortality, while treatment with a combination of appropriate antibiotics was identified as a predictor of good prognosis. Among septic shock patients (n = 74), Sequential Organ Failure Assessment (SOFA) score upon infection onset, adjunctive corticosteroid administration and strain carrying the blaKPC gene were independently associated with mortality, while the administration of combination treatment was identified as a predictor of a good prognosis. The administration of tigecycline predisposes to the induction of bacteraemia. Appropriate antibiotic treatment is associated with better survival, while concomitant corticosteroid treatment is associated with mortality.

Performance of four different agar plate methods for rectal swabs, synergy disk tests and metallo-β-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-β-lactamase positive and 3 K. pneumoniae carbapenemase and Verona integron-encodedmetallo-β-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-β-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-β-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.

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.

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.

Acute brucellosis presenting as cellulitis.

Sir, Brucellosis, a worldwide anthropozoonosis, is an infectious disease caused by bacteria of the genus Brucella, a Gram-negative, facultative intracellular pathogen affecting a wide range of mammals, including domestic animals and humans. The heaviest burden of this disease lies in countries of the Mediterranean basin and Arabian Peninsula, northern and eastern Africa, Near Eastern countries, central Asia, Mexico, and Central and South America. It is transmitted to humans mainly through ingestion of infected unpasteurized raw milk or dairy products, but also subsequent to direct contact with infected animals or, rarely, humans, and through the inhalation of contaminated particles. Human brucellosis is a systemic disorder with protean clinical manifestations, the diagnosis of which represents a great challenge to physicians and is definitely established through the isolation of Brucella spp. from clinical specimens and the detection of specific antibodies (1). The purpose of this paper is to draw attention to the presentation of acute brucellosis as cellulitis, which to the best ofour knowledge, has not been reported previously.