Effect of transient BK viremia and viruria on long-term renal allograft survival and function.

INTRODUCTION: The purpose of this study is to present the five-year survival and function of the renal allograft of recipients who were diagnosed with BK viremia and viruria during the first year after renal transplantation. PATIENTS AND METHODS: BK virus was studied in 32 new renal allograft recipients, from the first postoperative day until 18 months after the transplantation. Real-time polymerase chain reaction was used to detect and quantitate BK viral load in serum and urine samples. RESULTS: Qualitative analysis with PCR for the DNA of BK virus showed 31 (31/228, 14%) positive serum samples originating from 20 (20/32, 62%) renal allograft recipients and 57 (57/228, 25%) positive urine samples originating from 23 (23/32, 72%) recipients. During the follow up period of 5 years, renal allograft function remained stable (eGFR 18(th) month: 53.9 ± 23.9 mL/min/1.73 m(2) and eGFR 5(th) year: 52.6 ± 20.6 mL/min/1.73 m(2)). Comparison of recipients that presented with either BK viremia or viruria with a group that did not present viral reactivation did not reveal a statistically significant difference in eGFR. Furthermore, recipients with significantly high viral load in serum or urine did not present renal allograft dysfunction. CONCLUSION: BK virus is potentially pathogenic in renal allograft recipients. It is certain that there is a reactivation of the virus in a high percentage of transplanted patients mostly in the first year after the surgery, without however a negative effect of the transient viremia and viruria in renal allograft function.

Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins.

OBJECTIVES: This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. METHODS: A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. RESULTS: Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. CONCLUSIONS: Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.

Carbapenem-resistant versus carbapenem-susceptible Acinetobacter baumannii bacteremia in a Greek intensive care unit: risk factors, clinical features and outcomes.

BACKGROUND: There has been an increasing incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) infections in recent years. The objective of this study was to determine specific risk factors for and outcome of bacteremia due to CRAB isolates among our ICU patients with A. baumannii bacteremia. PATIENTS AND METHODS: Among 96 patients with ICU-acquired A. baumannii bacteremia, 30 patients with CRAB were compared with the remaining 66 with carbapenem-susceptible A. baumannii (CSAB) isolates. RESULTS: Recent ventilator-associated pneumonia (VAP) due to CRAB (OR 16.74, 95% CI 3.16-88.79, p = 0.001) and a greater number of intravascular devices (OR 3.93, 95% CI 1.9-13.0, p = 0.025) were independently associated with CRAB bacteremia acquisition. Patients with CRAB bacteremia had a lower severity of illness on admission than those with CSAB. Although, by univariate analysis, patients with CRAB were more likely to have had exposure to colistin, carbapenems and linezolid, multivariate analysis did not revealed any significant association. The mortality was not different between patients with CRAB and CSAB bacteremia (43.3 vs. 46.9%, p = 0.740). Severity of organ failure (OR 1.42, 95% CI 1.20-1.67, p = 0.001), and increased white blood cell (WBC) count (OR 1.09, 95% CI 1.01-1.19, p = 0.036), at bacteremia onset were independently associated with mortality. CONCLUSION: VAP due to CRAB and excess use of intravascular devices are the most important risk factors for CRAB bacteremia in our ICU. Severity of organ failure and WBC count at A. baumannii bacteremia onset are independently associated with mortality.

Risk factors for and influence of bloodstream infections on mortality: a 1-year prospective study in a Greek intensive-care unit.

To determine the incidence, risk factors for, and the influence of bloodstream infections (BSIs) on mortality of patients in intensive-care units (ICUs), prospectively collected data from all patients with a stay in an ICU >48 h, during a 1-year period, were analysed. Of 572 patients, 148 developed a total of 232 BSI episodes (incidence 16.3 episodes/1000 patient-days). Gram-negative organisms with high level of resistance to antibiotics were the most frequently isolated pathogens (157 strains, 67.8%). The severity of illness on admission, as estimated by APACHE II score (OR 1.07, 95% CI 1.04-1.1, P<0.001), the presence of acute respiratory distress syndrome (OR 3.57, 95% CI 1.92-6.64, P<0.001), and a history of diabetes mellitus (OR 2.37, 95% CI 1.36-4.11, P=0.002) were risk factors for the occurrence of BSI whereas the development of an ICU-acquired BSI was an independent risk factor for death (OR 1.76, 95% CI 1.11-2.78, P=0.015). Finally, the severity of organ dysfunction on the day of the first BSI episode, as estimated by SOFA score, and the level of serum albumin, independently affected the outcome (OR 1.44, 95% CI 1.22-1.7, P<0.001 and OR 0.47, 95% CI 0.23-0.97, P=0.04 respectively).

Prospective monitoring of BK virus replication in renal transplant recipients.

BACKGROUND: BK virus-associated nephropathy (BKVAN) can be diagnosed only with renal graft biopsy. Definitive diagnosis of BKVAN requires demonstration of BK virus (BKV) replication in renal allograft tissues. Non-invasive analysis of urine and blood is considered essential in screening renal transplant recipients. PATIENTS AND METHODS: This study evaluated prospectively the replication of BKV in plasma and urine with qualitative and quantitative real-time polymerase chain reaction in 32 de novo (group A) and 34 chronic (group B) renal transplant recipients and the long-term impact on graft function. RESULTS: In group A, 456 samples (228 plasma, 228 urine) were examined and BKV was detected in 31 (31/228, 14%) samples of plasma and 57 (57/228, 25%) samples of urine in 20 (20/32, 62.5%) and 23 (23/32, 72%) recipients, respectively. Incidence of viremia and viruria increased during the first 6 months presenting a peak the third postoperative month (viremia: 28% and viruria: 31%). Immune suppressive treatment with tacrolimus showed significant relation with viremia. Renal graft function in de novo renal transplant recipients remained stable throughout the follow-up period without influence of BKV replication. In group B, incidence of viremia and viruria were 3% (1/34) and 9% (3/34) correspondingly, indicating that after the first post-transplant year the risk of BKV re-activation is diminished. CONCLUSION: The highest incidence of BK viremia and viruria is observed the third post-transplantation month, confirming previously published studies in Europe and the United States, and long-term follow up shows that BKV replication decreases significantly after the third post-transplant month and even transient viremia or viruria does not have an impact on renal function.

Ongoing epidemic of blaVIM-1-positive Klebsiella pneumoniae in Athens, Greece: a prospective survey.

OBJECTIVES: To determine the current frequency and study the characteristics of VIM-1-producing Klebsiella pneumoniae isolates from bloodstream infections in Greek hospitals. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Application of the sequential organ failure assessment (SOFA) score to bacteremic ICU patients.

BACKGROUND: Patients admitted to intensive care units (ICUs) are at a high risk of acquiring blood stream infections. We examined whether SOFA score on ICU admission and on the day of bacteremia can predict the occurrence of bacteremia and the outcome of bacteremic ICU patients. PATIENTS AND METHODS: All patients admitted to a multidisciplinary ICU for more than 48 h from January 1, 2002 to December 31, 2004, were prospectively studied. Demographic, clinical and laboratory data were recorded on admission for all patients and additionally, on the day of the first bacteremic episode for those patients who developed bacteremia. Accordingly, APACHE II and SOFA scores were calculated on the same day. RESULTS: A total of 185 patients developed one or more episodes of bacteremia, giving an incidence of 9.6 per 1,000 ICU days. The ICU mortality rate was 43.9% for bacteremic and 25.8% for the remaining patients (p < 0.001). Admission SOFA score was independently associated with the occurrence of bacteremia (OR = 1.20, 95% CI: 1.11-1.26, p < 0.001). Among bacteremic patients, SOFA score on the day of bacteremia was the only independent prognostic factor for outcome (OR = 1.44, 95% CI: 1.21-1.71, p < 0.001). When all patients were included in the multivariate analysis, admission SOFA (OR = 1.3, CI: 1.16-1.38, p < 0.001), APACHE II (OR = 1.1, CI: 1.02-1.11, p = 0.003) score and the presence of bacteremia (OR = 1.8, CI: 1.1-2.9, p = 0.023) were independently associated with the outcome. CONCLUSION: Admission SOFA score is independently associated with the occurrence of ICU-acquired bacteremia, whereas it is not sufficient to predict the outcome of patients who subsequently will develop this complication. However, SOFA score on the first day of bacteremia is an independent prognostic factor for outcome in these patients.

Infective endocarditis in Greece: a changing profile. Epidemiological, microbiological and therapeutic data.

The epidemiology, and clinical and microbiological spectrum, of infective endocarditis (IE) in Greece was analysed in a prospective 4-year study in a tertiary hospital and a heart surgery centre in Athens. In total, 101 cases of IE (71 men, 30 women, aged 54.4 +/- 17.1 years) were studied, with a follow-up period of 3 months. Seventy-seven cases were definite and 24 possible; 59 involved native valves (native valve endocarditis; NVE), 31 prosthetic valves (prosthetic valve endocarditis; PVE), of which nine were early and 22 late, and 11 permanent pacemakers (pacemaker endocarditis; PME). There was a predominant involvement of aortic (48/101) and mitral (40/101) valves. Seven patients had rheumatic valvular disease, two had mitral valve prolapse, and eight had a previous history of IE. Thirteen and six patients had undergone dental and endoscopic procedures, respectively. In 13 patients, intravenous catheters were used within the 3 months before diagnosis of IE. There were three intravenous drug users among the patients. Staphylococcus aureus was the most important pathogen, isolated in 22% of cases, followed by viridans streptococci (19%) and coagulase-negative staphylococci (16%). Enterococcus spp. were responsible for 3%, HACEK group for 2%, and fungi for 6% of cases. Viridans streptococci were the leading cause of NVE (29%), Staphylococcus epidermidis of PVE (16%), and S. aureus of PME (54.5%). Six of 22 S. aureus and ten of 16 S. epidermidis isolates were methicillin-resistant. Surgical intervention, including total pacemaker removal, was performed in 51.5% of patients. Overall mortality was 16%, but was 29% with PVE, and was significantly higher with medical than with combined surgical and medical therapy (24.5% vs. 8%). Compared with previous studies, there were changing trends in the epidemiology, microbiology, treatment and prognosis of IE in Greece.

Detection of enterococcal surface protein gene (esp) and amplified fragment length polymorphism typing of glycopeptide-resistant Enterococcus faecium during its emergence in a Greek intensive care unit.

The emergence of glycopeptide-resistant Enterococcus faecium (GREF) in a Greek intensive care unit was studied by amplified fragment length polymorphism analysis and esp gene detection. Three GREF clones harboring the esp gene were recovered from 17 out of 21 patients, indicating the dissemination of genetically homogenous and virulent strains of GREF.

Bacterial susceptibilities to piperacillin/tazobactam in a tertiary care hospital: 5-year review.

Several factors influence the speed of development of antibacterial resistance, among which is the amount of antibiotic consumption. During the 3-year period 1998-2000, the consumption of piperacillin/tazobactam (pip/tazo) increased by 85% in our hospital. Five years ago we conducted a comparative in vitro study to evaluate susceptibilities of microorganisms to pip/tazo. The objective of the present study was to re-evaluate in vitro susceptibilities to pip/tazo, compared to other beta-lactams, and the potential impact its increased consumption might have on its susceptibility patterns. The study was performed between November 2000 and April 2001. As in 1996, of the beta-lactams studied, pip/tazo and imipenem had the highest susceptibility rates against selected pathogens (>90% susceptibility rates). P. aeruginosa susceptibilities to both imipenem and pip/tazo were high (97% for both). P. aeruginosa susceptibilities to cefepime were lower. Despite its increased use, pip/tazo retained its initially observed high susceptibility rates for the study pathogens.

Extended-spectrum beta-lactamase types in Klebsiella pneumoniae and Escherichia coli in two Greek hospitals.

Seventy-nine Klebsiella pneumoniae and 124 Escherichia coli clinical strains, isolated consecutively during August-October 2001 in two Greek hospitals, were examined for production of extended-spectrum beta-lactamases (ESBLs). Seventy-one (35%) isolates (46 K. pneumoniae and 25 E. coli) were ESBL-positive by phenotypic methods. Isoelectric focusing of beta-lactamases and PCR assays for bla genes showed that SHV-5-type ESBLs were the most frequent (45 isolates, 22%) followed by CTX-M (24 isolates, 12%) and IBC (three isolates, 1.5%). The latter two ESBL types may have been established recently in this setting.

Aspergillus bronchitis causing atelectasis and acute respiratory failure in an immunocompromised patient.

Aspergillus tracheobronchitis is an uncommon clinical form of invasive aspergillosis with fungal infection limited entirely or predominantly to the tracheobronchial tree. We report a case of Aspergillus fumigatus bronchitis, diagnosed by fiberoptic bronchoscopy, with fungal growth completely occluding the left main bronchus leading to lung collapse and acute respiratory failure in a 60-year-old male with erythroleukemia and profound granulocytopenia.

Enterococcal infections in a Greek intensive care unit: a 5-y study.

In this study we determined the incidence, resistance pattern, and mortality rate associated with infection caused by Enterococcus faecalis and Enterococcus faecium among patients in a multidisciplinary intensive care unit (ICU). A total of 111 patients with E. faecalis and 60 with E. faecium infections were identified during a 5-y period (1992-96). We observed an increase in the incidence of enterococcal infections (from 5.46 to 8.46 per 1000 patients-days, p = 0.0112), due mainly to the increased incidence of E. faecium (from 0.45 to 4.06 per 1000 patients-days, p = 0.002). Blood was the most common site of enterococcus isolation. E. faecium was more resistant to antibiotics than E. faecalis, but no vancomycin resistant enterococcus was isolated. Patients with E. faecium infection had a significantly higher mortality than patients with E. faecalis infection (66% vs. 41.5%, p = 0.0035 for infection from any site and 85.7 vs. 47.7%, p = 0.012 for bacteremic patients). r 4n- D I .- .- - .. . .

Liver and brain mucormycosis in a diabetic patient type II successfully treated with liposomial amphotericin B.

A case of liver and brain mucormycosis in a 73-y-old diabetic patient is described. The patient presented with fever and a moderate, tender hepatomegaly and a C/T scan examination of the abdomen and brain showed multiple hepatic and cerebral nodular lesions. The largest of the liver lesions was aspirated and broad hyphae of mucor were demonstrated in the purulent material obtained. The patient was treated successfully (for 40 d) with intravenous liposomal amphotericin B and then with itraconazole for 3 months. To our knowledge, this is the first case of a diabetic patient with both liver and brain mucormycosis who has been treated successfully.

Management and outcome of severe diabetic foot infections.

We evaluated the bacteriological and clinical efficacy of the combination of ciprofloxacin/clindamycin in severe diabetic foot infections and we tried to elucidate the relationship between the vascular status of the lower limbs and the outcome of these infections. Initial empirical antibiotic therapy with ciprofloxacin (300 mg/12 hrs IV) and clindamycin (600 mg/8 hrs IV) was administered in 84 hospitalized diabetics with severe lower limb infections. This treatment was continued only in cases with primary clinical improvement. The major endpoints of treatment were: cure, improvement and failure. Evaluation of the vascular status of the lower extremities was performed by high resolution imaging coloured ultrasonography, US-Doppler and TcPO2 measurements. Polymicrobial flora was found in 83% of the cases with an average 2.8 species per specimen. Osteomyelitis was detected in 58 % of the patients. After five days of IV administration of ciprofloxacin and clindamycin the response rate was 95.2%. After three weeks of therapy the clinical outcome was: cure 54.8%, improvement 23.8%, and failure 21.4%. The long term follow up (mean duration 16 months) revealed complete healing of the skin lesions in 63 patients (75%). Unfavorable prognostic factors for these infections were: ankle systolic blood pressure <50 mmHg or toe systolic blood pressure < 30 mmHg and TcPO2 < 20 mmHg. The side effects of the combination of ciprofloxacin/clindamycin were mild and there were no cases of pseudomembranous enterocolitis. The combination of ciprofloxacin/clindamycin was found to provide an excellent empirical as well as definitive treatment of severe diabetic foot infections. The evaluation of the vascular status and the severity of ischaemia of the lower limbs has a strong predictive value in the outcome of these infections.