[Show abstract][Hide abstract] ABSTRACT: The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) is essential for maintenance of enzymatic function. We hypothesized that induction of BH4 synthesis might be an endothelial defense mechanism against inflammation in vascular disease states.
In Study 1, 20 healthy individuals were randomized to receive Salmonella typhi vaccine (a model of acute inflammation) or placebo in a double-blind study. Vaccination increased circulating BH4 and interleukin 6 and induced endothelial dysfunction (as evaluated by brachial artery flow-mediated dilation) after 8 hours. In Study 2, a functional haplotype (X haplotype) in the GCH1 gene, encoding GTP-cyclohydrolase I, the rate-limiting enzyme in biopterin biosynthesis, was associated with endothelial dysfunction in the presence of high-sensitivity C-reactive protein in 440 coronary artery disease patients. In Study 3, 10 patients with coronary artery disease homozygotes for the GCH1 X haplotype (XX) and 40 without the haplotype (OO) underwent S Typhi vaccination. XX patients were unable to increase plasma BH4 and had a greater reduction of flow-mediated dilation than OO patients. In Study 4, vessel segments from 19 patients undergoing coronary bypass surgery were incubated with or without cytokines (interleukin-6/tumor necrosis factor-α/lipopolysaccharide) for 24 hours. Cytokine stimulation upregulated GCH1 expression, increased vascular BH4, and improved vasorelaxation in response to acetylcholine, which was inhibited by the GTP-cyclohydrolase inhibitor 2,4-diamino-6-hydroxypyrimidine.
The ability to increase vascular GCH1 expression and BH4 synthesis in response to inflammation preserves endothelial function in inflammatory states. These novel findings identify BH4 as a vascular defense mechanism against inflammation-induced endothelial dysfunction.
[Show abstract][Hide abstract] ABSTRACT: We explored the role of asymmetrical dimethylarginine (ADMA) as a cause of endothelial dysfunction induced by systemic inflammation. In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli, but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans. In study 1 we recruited 351 patients with coronary artery disease (CAD) and 87 healthy controls. In study 2 we recruited 69 CAD, 69 healthy, and 10 patients with rheumatoid arthritis, whereas in study 3, 22 healthy and 70 CAD subjects were randomly assigned to Salmonella typhii vaccination (n=11 healthy and n=60 CAD) or placebo (n=11 healthy and n=10 CAD). Circulating interleukin 6/ADMA and flow-mediated dilation (FMD) were measured at 0 and 8 hours. In study 1, ADMA was inversely correlated with FMD in healthy individuals and CAD patients (P<0.0001 for both). However, interleukin 6 was inversely correlated with FMD (P<0.0001) in healthy subjects but not in CAD patients. The positive correlation between ADMA and interleukin 6 was stronger in healthy (r=0.515; P<0.0001) compared with CAD (r=0.289; P=0.0001) subjects. In study 2, both patients with rheumatoid arthritis and CAD had higher interleukin 6 (P<0.0001) and ADMA (P=0.004) but lower FMD (P=0.001) versus healthy subjects. In study 3, vaccination increased interleukin 6 in healthy (P<0.001) and CAD (P<0.001) subjects. FMD was reduced in healthy subjects (P<0.05), but its reduction in CAD was borderline. Vaccination increased ADMA only in healthy subjects (P<0.001). Systemic, low-grade inflammation leads to increased ADMA that may induce endothelial dysfunction. This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans.
[Show abstract][Hide abstract] ABSTRACT: Nosocomial infections are a frequent and continuously increasing problem worldwide, have a rapidly increasing multidrug resistance to antibiotics, and are associated with significant morbidity and mortality.
Our objectives were to evaluate Acinetobacter baumannii infection incidence in our surgical intensive care unit (SICU), the clinical features and outcome of these patients, and, particularly, to investigate predictors of A baumannii infection-related mortality.
Ours was a prospective study of all patients with ICU-acquired A baumannii infection from January 1, 2006, to December 31, 2007.
Among 680 patients, 60 (8.8%) sustained A baumannii infection. Mean age was 68.4 ± 6.2 years, Acute Physiology and Chronic Health Evaluation (APACHE) II score on SICU admission 20.6 ± 8.1 and Sequential Organ Failure Assessment (SOFA) score on infection day 9.5 ± 4.2 (women: 50%). Multidrug resistance, morbidity, and mortality were 45%, 65%, and 46.6% (n = 28), respectively. In multivariate analysis, age (P = .03; odds ratio [OR], 1.13; 95% confidence interval [CI]: 1.018-1.259), acute renal failure (P = .001; OR, 17.9; 95% CI: 6.628-75.565), and thrombocytopenia (P = .03; OR, 26.4; 95% CI: 1.234-56.926) complicating the infection and subsequent Enterococcus faecium bacteremia (P = .01; OR, 3.5; 95% CI: 1.84-6.95) were mortality predictors.
A baumannii infections are frequent and associated with high drug multiresistance, morbidity, and mortality. Age, renal failure, thrombocytopenia, and subsequent E faecium bacteremia were predictors of A baumannii infection-associated mortality.
American journal of infection control 10/2010; 38(8):631-5. DOI:10.1016/j.ajic.2010.01.009 · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity is associated with impaired postprandial triacylglycerolemia, an independent risk factor for cardiovascular disease. Given that obesity is hard to treat, efforts should focus on treating its comorbidities. We aimed to investigate whether moderate weight loss normalizes postprandial triacylglycerol (TAG) concentrations, in the absence of the acute effects of negative energy balance. For this purpose, postprandial lipemia was investigated in eight obese but otherwise healthy, sedentary men (age: 41.3 ± 4.1 years, BMI: 36.5 ± 1.6 kg·m(-2)), once before and again after a 10% weight loss followed by ≥4 weeks of weight maintenance, and was compared with that of eight age-matched healthy lean men (BMI: 24.7 ± 0.6 kg·m(-2)). Dietary intervention consisted of reduced carbohydrate and saturated fat intake and increased monounsaturated fat intake. Obese volunteers were advised to increase physical activity using pedometers to record daily activity. Postprandial triacylglycerolemia after weight loss was reduced by 27-46% (P < 0.05), and became similar to that of lean men despite persisting obesity (BMI after weight loss: 32.9 ± 1.5 kg·m(-2)). Reduction in postprandial TAG responses was inversely correlated with the decrease in postprandial insulin sensitivity index (ISI) after weight loss (r = -0.714, P = 0.047). We conclude that moderate weight loss induced by a low-carbohydrate and saturated fat diet and a slight increase in daily physical activity normalizes postprandial triacylglycerolemia in obese men, independently of acute diet-induced negative energy balance, and possibly through enhancement of insulin action.
[Show abstract][Hide abstract] ABSTRACT: Fungal peritonitis is a rare, potentially lethal, complication of continuous ambulatory peritoneal dialysis (CAPD). We report what we believe to be the first confirmed Neosartorya hiratsukae CAPD-related peritonitis case in Europe. The patient died, despite early removal of the peritoneal catheter and antifungal therapy. This report highlights the impact of emerging fungal pathogens and the importance of early diagnosis on the outcome in CAPD-related fungal peritonitis.
Journal of Medical Microbiology 07/2010; 59(Pt 7):862-5. DOI:10.1099/jmm.0.019133-0 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Blood lipids and inflammatory markers levels have been associated with the development and progression of atherosclerosis. As the association of inflammatory markers with plasma fatty acids has not been extensively evaluated and understood, we sought to investigate the associations between dietary and plasma fatty acids with various inflammation and coagulation markers.
High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), fibrinogen, and homocysteine were measured in serum of 374 free-living, healthy men and women, randomly selected from the ATTICA's study database. Total plasma fatty acids were determined by gas chromatography. Dietary fatty acids were assessed through a semi-quantitative FFQ.
Multi-adjusted regression analyses revealed that plasma n-3 fatty acids were inversely associated with CRP, IL-6 and TNF-alpha; plasma n-6 fatty acids were inversely associated with CRP, IL-6 and fibrinogen; monounsaturated fatty acids were inversely associated with CRP and IL-6 (all p-values<0.05). Interestingly, the n-6/n-3 ratios exhibited the strongest positive correlations with all the markers studied. No associations were observed between dietary fatty acids and the investigated markers.
Measurements of total plasma fatty acids could provide insights into the relationships between diet and atherosclerotic disease. Moreover, the n-6/n-3 ratio may constitute a predictor of low-grade inflammation and coagulation.
Clinica chimica acta; international journal of clinical chemistry 04/2010; 411(7-8):584-91. DOI:10.1016/j.cca.2010.01.023 · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to evaluate the clinical and microbiological characteristics of the patients who developed an infection in our surgical intensive care unit (SICU).
This was a prospective study of all patients who sustained an ICU-acquired infection from 2002 to 2004.
Among 683 consecutive SICU patients, 123 (18.0%) developed 241 infections (48.3 infections per 1000 patient-days). The mean age of patients was 66.7+/-3.8 years, the mean APACHE II score (acute physiology and chronic health evaluation) on SICU admission was 18.2+/-2.4, and the mean SOFA score (sepsis-related organ failure assessment) at the onset of infection was 8.8+/-2. Of the study patients, 51.2% were women. Infections were: bloodstream (36.1%), ventilator-associated pneumonia (VAP; 25.3%, 20.3/1000 ventilator-days), surgical site (18.7%), central venous catheter (10.4%, 7.1/1000 central venous catheter-days), and urinary tract infection (9.5%, 4.6/1000 urinary catheter-days). The most frequent microorganisms found were: Acinetobacter baumannii (20.3%), Pseudomonas aeruginosa (15.7%), Candida albicans (13.2%), Enterococcus faecalis (10.4%), Klebsiella pneumoniae (9.2%), Enterococcus faecium (7.9%), and Staphylococcus aureus (6.7%). High resistance to the majority of antibiotics was identified. The complication and mortality rates were 58.5% and 39.0%, respectively. Multivariate analysis identified APACHE II score on admission (odds ratio (OR) 4.63, 95% confidence interval (CI) 2.69-5.26, p=0.01), peritonitis (OR 1.85, 95% CI 1.03-3.25, p=0.03), acute pancreatitis (OR 2.27, 95% CI 1.05-3.75, p=0.02), previous aminoglycoside use (OR 2.84, 95% CI 1.06-5.14, p=0.03), and mechanical ventilation (OR 3.26, 95% CI: 2.43-6.15, p=0.01) as risk factors for infection development. Age (OR 1.16, 95% CI 1.01-1.33, p=0.03), APACHE II score on admission (OR 2.53, 95% CI 1.77-3.41, p=0.02), SOFA score at the onset of infection (OR 2.88, 95% CI 1.85-4.02, p=0.02), and VAP (OR 1.32, 95% CI 1.04-1.85, p=0.03) were associated with mortality.
Infections are an important problem in SICUs due to high incidence, multi-drug resistance, complications, and mortality rate. In our study, APACHE II score on admission, peritonitis, acute pancreatitis, previous aminoglycoside use, and mechanical ventilation were identified as risk factors for infection development, whereas age, APACHE II score on admission, SOFA score at the onset of infection, and VAP were associated with mortality.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 10/2008; 13(2):145-53. DOI:10.1016/j.ijid.2008.05.1227 · 1.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the efficacy and the safety of combining high doses of statins and ezetimibe in heterozygous familial hypercholesterolemia (hFH) patients. Seventy patients with hFH, received 10 mg of ezetimibe, in addition to their current statin therapy and were followed up for twelve months. The co-administration of statins and ezetimibe improved total cholesterol (p<0.05), LDL-c(p<0.05), triglycerides (p<0.05) and apolipoprotein-B (p<0.05) in comparison to statin monotherapy. There were no changes in high density lipoprotein cholesterol (HDL-c), apolipoprotein-A, lipoprotein (a), fibrinogen and C-reactive protein (CPR). In conclusion the combination of 10 mg of ezetimibe with high dose statin therapy is effective in hFH, offering a further reduction of LDL-c throughout the 12 months of follow up.
International journal of cardiology 03/2008; 134(2):280-1. DOI:10.1016/j.ijcard.2007.12.065 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human adult cardiomyocytes (CM) have been used in short-term cultures for in vitro studies of the adult myocardium. However, little information is available regarding human adult CMs cultured for long term (>2 weeks).
Human adult CMs were isolated from atrial specimens of 43 patients undergoing cardiopulmonary bypass surgery. Cell viability, cytoskeletal properties, intercellular junctional mediators and responsiveness to extracellular stimuli were monitored in CM cultures for 8 weeks.
Absolute numbers of CMs decreased through the first 2 weeks, with substantially lower rates of cell loss thereafter. Apoptosis predominated over necrosis as the principal mode of cell death, affecting 4.1+/-1.6% of freshly dissociated cells, that declined in culture (3.6+/-1.0% week 1, 1.3+/-0.5% week 2). CMs maintained rod-shaped morphology and cross-striated expression pattern of sarcomeric proteins desmin and beta-myosin heavy chain for the first 4 weeks. Levels of desmin remained stable on first 3 weeks, but declined thereafter. CMs expressed cardiac-specific adherence molecule N-cadherin throughout the culture duration, indicating conserved contractile potential. CMs remained functional early in culture, as indicated by BNP secretion, with maximal levels on 1st week that declined gradually by week 4. Cell responsiveness to metabolic stresses (serum deprivation) was detected, inducing an early (6 h) 1.8-fold increase in levels of BNP.
Long-term cultured human adult CMs maintain morphological integrity, adult-type cytoskeletal protein expression, cell-cell communication potential and functionality for 3-4 weeks in vitro.
International journal of cardiology 03/2008; 131(1):113-22. DOI:10.1016/j.ijcard.2007.10.058 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cardioprotective role of hormonal replacement therapy remains in doubt, but interest is increasing in the vascular effects of estrogens especially in coronary circulation.
Coronary blood flow (CBF) was measured in 24 postmenopausal women (age 55+/-3 years), whose coronary arteries appeared angiographically normal, during incremental atrial pacing (AP) before and 20 minutes after intracoronary administration of either 75 ng/mL 17-beta estradiol (treated group, n=18) or 0.9% saline (controls, n=6).
Before estrogen, no differences in the coronary vasomotor responses at AP between the two groups (p=NS) could be detected. After estrogen, in the treated group, at the peak of the second AP, the coronary artery diameter decreased by 0.17 mm (p<0.005) while the CBF increased by 61 mL/min (p<0.05). These changes differed significantly from those observed at the peak of first AP (p<0.001 for both cases). In contrast, in the control group no such changes were observed. The endothelin-1 (ET-1) levels in the coronary sinus were significantly reduced after estrogen infusion, which was negatively correlated with the degree of coronary artery constriction (r= -0.40, p=0.03) and positively correlated with the increase in CBF (r=0.54, p=0.01).
In postmenopausal women without coronary artery disease, the intracoronary estrogen infusion mediates a greater increase in CBF and is positively correlated with the reduction of the coronary sinus ET-1 levels at the peak of AP.
Vascular Health and Risk Management 02/2008; 4(3):705-14.
[Show abstract][Hide abstract] ABSTRACT: To determine the current frequency and study the characteristics of VIM-1-producing Klebsiella pneumoniae isolates from bloodstream infections in Greek hospitals.
All blood isolates of K. pneumoniae were prospectively collected during 2004-06 in three teaching hospitals located in Athens. MICs of antibiotics were determined by the Etest. Extended-spectrum- (ESBL) and metallo-beta-lactamase (MBL) production was examined by clavulanate- and EDTA-based techniques, respectively. Isolates were typed by PFGE of XbaI-digested genomic DNA. Detection of bla(VIM-1) and mapping of the VIM-1-encoding integrons were performed by PCR and sequencing. Beta-lactamase activities were analysed by IEF and imipenem hydrolysis was assessed by spectrophotometry. VIM-1-encoding plasmids were transferred to Escherichia coli by conjugation and transformation and characterized by Inc/rep typing and RFLP.
Sixty-seven (37.6%) of 178 K. pneumoniae blood isolates were bla(VIM-1)-positive (VPKP); 77.8% of these were from ICUs. All VPKP isolates were multidrug-resistant. The MICs of carbapenems for VPKP varied from the susceptible range to high-level resistance overlapping with those of MBL-negative isolates. The EDTA-imipenem synergy methods had reduced sensitivity in detecting VPKP isolates when the MICs were in the susceptible range. ESBL production was common among VPKP isolates (n = 45, 67.2%) as indicated by resistance to aztreonam and confirmed by a clavulanate-based double-disc synergy test. The responsible ESBL was always an SHV-5-type enzyme as indicated by IEF. PFGE identified eight clusters (A-H) of VPKP isolates with related (>80%) patterns, as well as four unique types. Both inter-hospital spread of several clones and genotypic similarities among susceptible, ESBL-positive and VPKP isolates were also observed. Location of bla(VIM-1) and expression of VIM-1 were studied in 12 isolates representing the eight PFGE clusters. In all isolates, bla(VIM-1) was part of a class 1 integron that also carried aacA4, dhfrI, aadA and sulI. In eight isolates (clusters C, D, G and H), the bla(VIM-1) integron was located in transferable IncN plasmids. A cluster F isolate carried a VIM-1-encoding, self-transferable plasmid that was not typeable by Inc/rep typing. VIM-1-encodingreplicons were not identified in three isolates (PFGE clusters A, B and E). VPKP isolates exhibited differences in imipenem-hydrolysing activities which, however, were not correlated with the respective carbapenem MICs.
A multiclonal epidemic of bla(VIM-1)-carrying K. pneumoniae is under way in the majorhospitals in Greece. Microorganisms producing both VIM-1 and SHV-5 constitute the prevalent multidrug-resistant population of K. pneumoniae in this setting.
[Show abstract][Hide abstract] ABSTRACT: Familial combined hyperlipidaemia (FCH) is an inherited dyslipidaemia that is related to a high risk of coronary artery disease (CAD). We evaluated the prevalence of CAD in a large FCH population and the association of risk factors with CAD according to gender.
In this single-center, observational study, lipid and lipoprotein variables were measured in untreated patients with FCH (565 males and 302 females). CAD was defined as a documented history of myocardial infarction or coronary revascularization, or an abnormal coronary angiogram (stenosis of >50% in an epicardial coronary artery), or angina plus abnormal imaging stress test.
Males had higher triglyceride level (P<0.001) but lower total cholesterol (P<0.001) and HDL-cholesterol level (P<0.001) compared to women. The prevalence of CAD was 22.2% in men and 4.6% in women (P<0.001). In logistic regression analysis, male gender was associated with a higher risk of CAD independent of lipid parameters and other risk factors (adjusted ORs for CAD 9.4, P<0.001). In gender-specific analysis, age (OR=1.06 per 1-year increase, P<0.001), diabetes (OR=2.42, P<0.01) and Lp(a) (OR=1.09 per 1-mg/dL increase, P<0.01) were independent predictors of CAD in men. In women, age (OR=1.24, P<0.01), total cholesterol (OR=1.022 per 1-mg/dL increase, P<0.05) and fasting glucose (OR=1.031 per 1-mg/dL increase, P<0.05) were independently associated with CAD.
In FCH patients, the prevalence of CAD is higher in males than in females, independent of lipidaemic profile and other risk factors. Among lipid variables, Lp(a) and cholesterol level are predictors of CAD in males and females respectively.
[Show abstract][Hide abstract] ABSTRACT: Heterozygous familial hypercholesterolemia (hFH) and familial combined hyperlipidemia (FCH) have been associated with increased risk for coronary artery disease (CAD), but the impact of traditional risk factors to the incidence of CAD in these patients remains unknown. The present study evaluates the contribution of such risk factors to the development of CAD in these two dyslipidemic populations.
This cross-sectional study enrolled a total 1306 subjects; 600 individuals with hFH (mean age 41+/-13 years, 261 males and 339 females), and 706 individuals with FCH (mean age 49+/-11 years, 463 males and 243 females). Blood samples were collected after 12 hours fasting period, and serum lipids were determined. Multivariate logistic regression models were used to estimate the odds ratios of CAD based on the type of hyperlipidemia, after adjustment for demographic characteristics and risk factors.
Subjects with FCH were older (P<0.001), and they had a significantly increased prevalence of hypertension, diabetes and metabolic syndrome (40 vs. 10%, 13 vs. 2% and 41 vs. 6% respectively, all P<0.001) compared to the hFH group. Total cholesterol, LDL-cholesterol, and apolipoprotein B levels were higher (all P<0.001) in hFH subjects. Although in multivariate analysis lipid abnormalities found in hFH were associated with increased risk of CAD (P<0.001) compared with lipid abnormalities of FCH, the overall prevalence of CAD was similar between the two groups (16.7 vs. 15.3%, P=NS).
Despite the high atherogenic potential of altered lipid metabolism found in hFH, the prevalence of CAD is similarly increased in patients with hFH or FCH. This may be related to the clustering of non-lipid cardiovascular risk factors, such as diabetes mellitus, observed in patients with FCH.
International journal of cardiology 10/2007; 121(2):178-83. DOI:10.1016/j.ijcard.2006.11.005 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial combined hyperlipidemia (FCH) is closely related with metabolic syndrome (MetSyn), and coronary artery disease (CAD) is positively associated to MetSyn and FCH. In this study, we evaluated the prevalence of MetSyn and its components between patients with FCH and a control group. We also investigated the role of MetSyn and diabetes mellitus (DM) on the incidence of CAD within the FCH group. Our study population consisted of 463 male and 243 female patients with FCH who were not receiving any hypolipidemic treatment, and 1128 men and 1154 women who came from the same geographical region. The prevalence of MetSyn was 42% and 19.8% among FCH subjects and controls, respectively, whereas MetSyn increased with age in both groups. The prevalence of CAD was 15.3% in the FCH group. Moreover, after dividing FCH patients into 3 subgroups, with and without MetSyn and with DM, CAD prevailed at a percentage of 15.2%, 11.1%, and 26.5%, respectively. However, statistically significant differences in the prevalence of CAD were observed only between FCH subjects with DM compared with the other 2 subgroups, even when an adjustment for age, sex, and smoking was conducted. People with FCH and MetSyn differed in several anthropometric, biochemical, and clinical characteristics, compared with the non-MetSyn subgroup of FCH. MetSyn is more prevalent in the FCH than in the control group. Among subjects with FCH, only DM was significantly associated with an increase in the prevalence of CAD in this subgroup compared with FCH individuals with or without MetSyn.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the alterations of serum procalcitonin (PCT) levels in patients with chronic hepatitis C during pegylated interferon-alpha (PEG-IFNa) plus ribavirin (RIB) treatment and to correlate them with clinical and virological outcomes.
Fifty-two consecutive patients (29 males, age=41.2+/-14.7 years) with chronic HCV-related liver disease (six cirrhotics) were evaluated for PCT levels at baseline and during the treatment course (at week 12, 24, 48 and 72) with PEG-IFNa plus RIB. Sustained virological response (SVR) was confirmed by undetectable serum HCV-RNA at the end of treatment and again 6 months after completion of treatment.
Two patients exhibited culture-proved bacterial infections during the treatment course. Thirty-six patients (69.2%) exhibit SVR and 16 (30.8%) were non-responders. Serum PCT levels remained within normal limits (0.1-0.5 ng/mL) in all treated patients throughout the follow-up period except those two who exhibited bacterial infections during the treatment course. Virological responders exhibited significant decline of serum PCT levels over time compared to non-responders (p<0.001), even when adjusted for multiple baseline parameters (p=0.037).
Serum PCT levels decline in chronic hepatitis C patients during PEG-IFNa plus RIB treatment, especially in the sustained virological responder group, while they elevate only when bacterial infections complicate the treatment course.
[Show abstract][Hide abstract] ABSTRACT: Background: The aims of the study were to identify the factors associated with bloodstream infections caused by VIM-1-producing Klebsiella pneumoniae and to evaluate the clinical significance of this type of metallo-beta-lactamases (MBLs).
Methods: A prospective case-control study was conducted for 1.5-year in three tertiary care hospitals in Greece. Patients with bacteremia caused by Klebsiella pneumoniae were identified by blood culture report of microbiology laboratory and clinical information was abstracted in a pre-designed form. Production of MBL was detected by double disk diffusion test (imipenem/imipenem+EDTA) and all isolates were examined for the presence of blaVIM-1by PCR. Susceptibility testing to imipenem was performed with Etest. As cases were considered patients with VIM-1-producing Klebsiella pneumoniae bacteremia and as controls those with non-VIM-1-producing isolates.
Results: Kl. pneumoniae bacteremia was diagnosed in 183 patients. blaVIM-1was detected in 67 (36.6%) isolates, 42 (75%) of them from patients in ICU. The MICs of imipenem (IMP) were ≥8 μg/ml for 16 isolates. All non-VIM-1-producing isolates had MICs of IMP <0.25μg/ml. Hospitalization in ICU was independently associated with isolation of VIM-1-producing Klebsiella pneumoniae (OR, 4.9; 95% CI 1.4-17.2, P=0.01). Resistance to IMP (OR, 5.5; 95% CI 1.3-23.3, P= 0.019) and older age (OR, 1.0; 95% CI 1.0-1.0, P=0.022) were the only independent determinants of 14-day mortality.
Bloodstream infections by VIM-1-producing Klebsiella pneumoniae are associated with high mortality when the infecting organism exhibits resistance to imipenem.
Infectious Diseases Society of America 2006 Annual Meeting; 10/2006