Diamantis P. Kofteridis

Aerosolized plus Intravenous Colistin versus Intravenous Colistin Alone for the Treatment of Ventilator-Associated Pneumonia: A Matched Case-Control Study

OBJECTIVES The incidence of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) organisms is increasing. Intravenous (IV) colistin or aerosolized (AS) plus IV colistin have been recently used to treat these life-threatening infections. The purpose of this study was to compare the efficacy and safety of AS plus IV colistin versus IV colistin alone for patients with MDR VAP due to gram-negative bacteria. METHODS A retrospective matched case-control study was performed at the Intensive Care Unit of the University Hospital of Heraklion, Greece, from January 2005 through December 2008. Forty-three patients with VAP due gram-negative MDR pathogens received AS plus IV colistin and were matched on the basis of age and Acute Physiology and Chronic Health Evaluation II score with 43 control patients who had received IV colistin alone. RESULTS Demographic characteristics, clinical status, and gram-negative isolated pathogens were similar between the 2 treatment groups. Acinetobacter baumannii (66 cases [77%]) was the most common pathogen, followed by Klebsiella pneumoniae (12 cases [14%]) and Pseudomonas aeruginosa (8 cases [9.3%]). No colistin-resistant strains were isolated from patients in either group. No significant differences between the 2 groups were observed regarding eradication of pathogens (P = .679), clinical cure (P = .10), and mortality (P = .289). Eight patients (19%) in each treatment group developed reversible renal dysfunction. No AS colistin-related adverse events were recorded. CONCLUSIONS Addition of AS colistin to IV colistin did not provide additional therapeutic benefit to patients with MDR VAP due to gram-negative bacteria.

The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis.

Objectives:The present meta-analysis and systematic review evaluated the efficacy and safety of aerosolized colistin as adjunctive therapy to IV antimicrobials or as monotherapy in the treatment of ventilator-associated pneumonia. Design:The databases of MEDLINE and Cochrane Library up to June 2013 and all reference lists of the included studies and relevant reviews were searched. Studies were eligible if the efficacy and safety of aerosolized colistin in the treatment of ventilator-associated pneumonia was evaluated. An overall effect estimate for all dichotomous data as an odds ratio with 95% CI was calculated by the Mantel-Haenszel or the DerSimonian and Laird method depending on the statistical heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to interpret the findings. Interventions:None. Measurements and Main Results:Sixteen studies fulfilled the inclusion criteria: eight were comparing adjunctive aerosolized versus IV colistin (seven observational cohort or case-control studies and one randomized trial) and were meta-analyzed, and eight were single arm and were only systematically reviewed. The Grading of Recommendations Assessment, Development, and Evaluation approach showed limitations of the study design and presence of inconsistency in most of the outcomes, but no obvious indirectness or imprecision of results reporting. Based on the above assessments, the quality of evidence presented for each outcome ranged from “very low” to “low.” A significant improvement in clinical response (odds ratio, 1.57; 95% CI, 1.14–2.15; p = 0.006; I2 = 37%), microbiological eradication (odds ratio, 1.61; 95% CI, 1.11–2.35; p = 0.01; I2 = 0%), and infection-related mortality (odds ratio, 0.58; 95% CI, 0.34–0.96; p = 0.04; I2 = 46%) was observed with the addition of aerosolized colistin to IV treatment, whereas the addition of aerosolized colistin did not affect overall mortality (odds ratio, 0.74; 95% CI, 0.54–1.01; p = 0.06; I2 = 25%) or nephrotoxicity (odds ratio, 1.18; 95% CI, 0.76–1.83; p = 0.45; I2 = 0%). Conclusion:Based on the present results and awaiting further evidence from randomized trials, aerosolized colistin is associated with improved outcome in the treatment of ventilator-associated pneumonia although the level of evidence was low.

Stenotrophomonas maltophilia infections in a general hospital: patient characteristics, antimicrobial susceptibility, and treatment outcome.

Introduction Stenotrophomonas maltophilia is acquiring increasing importance as a nosocomial pathogen. Methods We retrospectively studied the characteristics and outcome of patients with any type of S. maltophilia infection at the University Hospital of Heraklion, Crete, Greece, between 1/2005–12/2010. S. maltophilia antimicrobial susceptibility was tested with the agar dilution method. Prognostic factors for all-cause in-hospital mortality were assessed with multivariate logistic regression. Results Sixty-eight patients (median age: 70.5 years; 64.7% males) with S. maltophilia infection, not related to cystic fibrosis, were included. The 68 patients were hospitalized in medical (29.4%), surgical (26.5%), hematology/oncology departments (23.5%), or the intensive care units (ICU; 20.6%). The most frequent infection types were respiratory tract (54.4%), bloodstream (16.2%), skin/soft tissue (10.3%), and intra-abdominal (8.8%) infection. The S. maltophilia-associated infection was polymicrobial in 33.8% of the cases. In vitro susceptibility was higher to colistin (91.2%), trimethoprim/sulfamethoxazole and netilmicin (85.3% each), and ciprofloxacin (82.4%). The empirical and the targeted treatment regimens were microbiologically appropriate for 47.3% and 63.6% of the 55 patients with data available, respectively. Most patients received targeted therapy with a combination of agents other than trimethoprim/sulfamethoxazole. The crude mortality and the mortality and the S. maltophilia infection-related mortality were 14.7% and 4.4%, respectively. ICU hospitalization was the only independent prognostic factor for mortality. Conclusion S. maltophilia infection in a general hospital can be associated with a good prognosis, except for the patients hospitalized in the ICU. Combination reigmens with fluoroquinolones, colistin, or tigecycline could be alternative treatment options to trimethoprim/sulfamethoxazole.

Epstein Barr Virus hepatitis

OBJECTIVES Epstein-Barr Virus (EBV) infection has the potential to establish life-long, benign infections in their hosts. Although biochemical evidence of hepatocellular damage is common, jaundice is uncommon and complete recovery is the rule. The present study describes clinical characteristics and changes of liver function tests during the course of infectious mononucleosis. PATIENTS AND METHODS All immunocompetent patients with hepatic dysfunction associated with acute EBV infection, cared for at the University Hospital of Heraklion, over a 6-year period, were identified and retrospectively studied. RESULTS The study included 41 patients with a median age of 18.5 (15-51) years. Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) were increased in an average maximum of 5-fold. Both transaminase levels started to rise 2 days after the clinical onset of the disease, and returned to normal after a period of 20 days. Alkaline-phosphatase (ALP), γ-glutamyltransferase (γ-GT) and bilirubin levels also increased above the normal values during the course of the disease and returned to normal after a period of 20, 30 and 22 days respectively. The changes of mean AST and ALT levels over time were statistically significant, while those of mean ALP, γ-GT and bilirubin levels over time were not. Anicteric cholestatic liver disease was observed in 24 patients (59%), while icteric only in 2 (6%). CONCLUSION Liver involvement in acute EBV infection represents mild and self-limited hepatitis with predominantly cholestatic features.

Caspofungin-non-susceptible Candida isolates in cancer patients

OBJECTIVES To identify the frequency of caspofungin-non-susceptible Candida isolates in cancer patients with candidiasis. METHODS We reviewed the in vitro susceptibilities (M27-A3 CLSI method) of 650 Candida spp. associated with invasive candidiasis episodes in 582 hospitalized cancer patients (2005-08). RESULTS AND CONCLUSIONS We identified seven caspofungin-non-susceptible Candida strains (three Candida tropicalis, two Candida glabrata and two Candida albicans) from 650 Candida isolates (1%). C. tropicalis (three out of seven) was the most common non-susceptible species isolated. All patients responded to a change of antifungal therapy. Further surveillance should focus on the potential broader emergence of echinocandin resistance, as the clinical use of this antifungal class continues to expand in cancer patients.

Incidence, Clinical, Microbiological Features and Outcome of Bloodstream Infections in Patients Undergoing Hemodialysis

Objectives: Infection is a common cause of death among hemodialysis patients. The study investigated incidence, risk factors, clinical features and outcome of bloodstream infections (BSIs) in haemodialysis patients. Methods: The records of haemodialysis patients from 1999 to 2005 were reviewed. Risk factors were investigated by multivariate analysis. Results: There were identified 148 bacteremic episodes, in 102 patients. The BSI rate was 0.52 per 1000 patient-days. Of the 148 episodes, 34 occurred in patients with permanent fistulae (0.18/1000 patient-days); 19 in patients with grafts (0.39/1000 patient-days); 28 in patients with permanent tunneled central catheters (1.03/1000 patient-days); and 67 in those with temporary-catheter (3.18/1000 patient-days). With fistula as reference, the BSI ratio was 1.84 with arteriovenous graft (P=.029), 4.85 with permanent central venous catheter (P<.001), and 14.88 with temporary catheter (P <.001). Catheter related were 41 episodes (28%). Gram positive organism were responsible for 96 episodes (65%), with S. aureus ( 55%) the most frequent, followed by S. epidermidis (26%) and Gram-negative for 36 (23%), with E. coli (39%) the most frequent. Infection was polymicrobial in 14 (9.5%). Diabetes (p<0.001), low serum albumin (p=0.040) and low hemoglobin (p<0.001) were significant risk factors. During hospitalization 18 patients (18%) died. Septic shock (p<0.001) and polymicrobial infection (p=0.041) were associated with in-hospital mortality. Conclusion: The risk of BSI in patients undergoing hemodialysis is related to the catheter type and vascular access. Septic shock and polymicrobial infection predispose to unfavourable outcome.

Effect of diabetes mellitus on the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis.

OBJECTIVES: To study potential differences in the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis with and without diabetes mellitus.

Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: A case–case-control study

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly reported worldwide. The aim of the present study was to identify risk factors associated with the development of CRKP infections. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece. The study population included 83 patients from whom CRKP was isolated, 79 from whom carbapenem-sensitive K. pneumoniae (CSKP) was isolated and 161 (control group) from whom K. pneumoniae was not isolated. The median age of CRKP and CSKP patients was 79 (28-101) and 80 (39-97) years, respectively, while that of the controls was 75 (18-100) years. K. pneumoniae was isolated predominantly from urine in both case groups, followed by blood. Independent risk factors for CRKP infection/colonization were admission to ICU (p = 0.004), prior surgical procedure (p = 0.036) and presence of renal disease (p = 0.037), while for CSKP were neurological disease (p = 0.007), and older age (p = 0.011). No association between CRKP and prior antimicrobial exposure was found. Of the entire cohort 40 patients (12%) died; 22 (27%) in the CRKP, 12 (15%) in the CSKP and 6 (4%) in the control group. Isolation of any K. pneumoniae strain was associated with higher mortality compared to the control group (21% vs. 4%; p < 0.005). Mortality was not statistically different between those infected/colonized/with a CRKP or a CSKP strain (p = 0.084). According to these results prior ICU stay, prior surgical procedure and renal disease were independent risk factors for the development of a CRKP infection/colonization.

Peritoneal dialysis-associated peritonitis: clinical features and predictors of outcome

OBJECTIVES The objective of this study was to identify the epidemiological, clinical, and microbiological factors affecting the outcome of peritoneal dialysis (PD)-associated peritonitis. METHODS All patients with PD-associated peritonitis, cared for at the University Hospital of Heraklion from 1990 to 2007, were retrospectively studied. RESULTS A total of 247 episodes of PD-associated peritonitis occurring in 82 patients were evaluated. The median age of patients was 68 years (range 10-92 years); 51 (62%) were males. There were 104 episodes (42%) of Gram-positive peritonitis, 46 (19%) of Gram-negative peritonitis, 13 (5%) of polymicrobial peritonitis, and 11 (4%) of fungal peritonitis. There were 64 (26%) complicated episodes. The latter included 22 (8.9%) relapses, 13 (5.3%) repeated episodes, 18 (7.3%) catheter removals, and 11 (4.5%) deaths. In multivariate analysis, the presence of a purulent exit-site infection (p<0.001), peritoneal dialysis effluent cell count >100 x 10(6)/l for more than 5 days (p<0.001), use of antimicrobials during the preceding 3 months (p<0.05), and low serum total protein level on admission (p<0.05) were independent predictors of a complicated course. CONCLUSIONS Exit-site infection, more than 5 days with a peritoneal dialysis effluent cell count >100 x 10(6)/l, prior use of antimicrobials, and low serum total protein level are potential predictors of complicated PD-associated peritonitis and may distinguish high-risk cases.

Bacteremic community-acquired pneumonia due to Pasteurella multocida

An 87-year-old man was admitted to hospital because of fever, productive cough, dyspnea and altered consciousness. His medical history was significant for chronic obstructive pulmonary disease. He owned several pets. Physical examination and a chest radiograph revealed right upper lobe pneumonia. Blood cultures taken on admission yielded Pasteurella multocida and antimicrobial susceptibility testing showed susceptibility to beta-lactams. The fever subsided four days after treatment with intravenous ceftriaxone and the patient was discharged in a very good clinical condition after two weeks of treatment. Although no history of bites or scratches was documented, it is likely that our patient was exposed to the secretions of his many pets through inhalation of contaminated aerosols. This resulted in tracheobronchial tree colonization by P. multocida, which later developed into pneumonia. Close animal contact should be avoided by frail, elderly patients with chronic pulmonary diseases, as it is a risk factor for pneumonia due to Pasteurella spp.