Omrum Uzun

Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from Turkey with OXA-48-like carbapenemases and outer membrane protein loss

Treatment options are limited in infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, with carbapenems generally preferred. Disturbingly, however, carbapenem-resistant strains are emerging worldwide. Here we report two clinical isolates, one Escherichia coli and one Klebsiella pneumoniae, each with high-level carbapenem resistance (imipenem minimum inhibitory concentration of 32 microg/mL). They were isolated following imipenem therapy from two hospital patients who had received imipenem therapy in different regions of Turkey. Both isolates produced OXA-48-like carbapenemases, enzymes so far reported only from Turkey. Both isolates also had group 1 CTX-M-type ESBLs and had lost major outer membrane proteins. OXA-48-like carbapenemases appear to be scattered in Turkey and surveillance to determine their prevalence is warranted.

Risk Factors and Predictors of Outcome in Patients with Cancer and Breakthrough Candidemia

Hematogenous candidiasis adds substantially to the morbidity and mortality rates of patients with cancer. Little is known about the risk factors and outcome in patients with breakthrough (BT) candidemia while on systemic antifungal therapy. All 479 episodes of candidemia in 474 consecutive patients with candidemia that was diagnosed at M. D. Anderson Cancer Center from 1988 through 1992 were studied retrospectively. A total of 49 patients had BT candidemia, defined as candidemia that developed after at least 5 days of systemic antifungal therapy. Risk factors for BT candidemia and predictors of mortality were investigated. Multivariate analysis revealed that intensive care unit stay, neutropenia, use of corticosteroids, and duration of neutropenia as significant risk factors for BT candidemia. Seventy-six percent of patients with BT candidemia died, compared with 50% of patients with non-BT infection. In multivariate analysis, intensive care unit stay, being and remaining neutropenic, APACHE III score, and disseminated disease were independent prognostic factors. In conclusion, identification of risk factors and predictors of a poor outcome in patients with cancer with BT candidemia may have important implications in early diagnosis and appropriate therapy of these patients.

Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin.

Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. Thirty patients received 200 mg of doxycycline plus 600 mg of rifampin once daily, and 31 patients were treated with 400 mg of ofloxacin plus 600 mg of rifampin once daily for 6 weeks. Nine patients in each group had complications of the disease. There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease.

Susceptibility testing of voriconazole, fluconazole, itraconazole and amphotericin B against yeast isolates in a Turkish University Hospital and effect of time of reading

Voriconazole is a promising azole effective against a variety of fungi, including yeasts. In this study, we tested in vitro activities of voriconazole, fluconazole, itraconazole and amphotericin B against some ATCC and reference strains and 250 clinical yeast isolates. We also evaluated the effect of time of reading on MIC results. Voriconazole was the most active agent against Candida and Trichosporon isolates, including the putatively fluconazole-resistant C. krusei (MIC(90) 0.25 microg/ml) and C. glabrata (MIC(90) 0.5 microg/ml). Amphotericin B MICs were scattered in a considerably narrow range in both RPMI 1640 and Antibiotic Medium 3. MICs at 24 hours and 48 hours were similar in general for all antifungals tested. The highest percentage of strains that showed 24-hour and 48-hour MICs within +/-1-log(2) dilution was observed for amphotericin B tested in RPMI (99%), and the lowest for amphotericin B tested in Antibiotic Medium 3 (80%). In conclusion, voriconazole is very effective against a wide spectrum of Candida species and 24-hour readings could substitute 48-hour MIC evaluation.

Epidemiology and Outcome of Fungemia in a Cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031)

BACKGROUND Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

European expert opinion on the management of invasive candidiasis in adults

This report discusses the present status of antifungal therapy and treatment options for candidaemia, considered by experts in the field in Europe. A conference of 26 experts from 13 European countries was held to discuss strategies for the treatment and prevention of invasive candidiasis, with the aim of providing a review on optimal management strategies. Published and unpublished comparative trials on antifungal therapy were analysed and discussed. Commonly asked questions about the management of candidaemia were selected, and possible responses to these questions were discussed. Panellists were then asked to respond to each question by using a touchpad answering system. After the initial conference, the viewpoint document has been reviewed and edited to include new insights and developments since the initial meeting. For many situations, consensus on treatment could not be reached, and the responses indicate that treatment is likely to be modified on a patient-to-patient basis, depending on factors such as degree of illness, prior exposure to azole antifungals, and the presence of potentially antifungal drug-resistant Candida species.

Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country

Sepsis continues to have a substantial mortality and morbidity despite advances in the diagnosis and management of this condition. We retrospectively analysed hospital charts of patients diagnosed to have sepsis between January 2002 and June 2003. Demographic characteristics of patients, microbiological findings and predictors of survival were evaluated. Sixty-nine sepsis episodes that occurred in 63 patients were analysed. The most common underlying diseases were hypertension, malignancies and diabetes mellitus. Renal insufficiency, respiratory distress and disseminated intravascular coagulation developed in 52.2, 30.4 and 30.4% of the episodes respectively; 47.7% of the blood cultures yielded an organism. Gram-negative bacteria were the predominant microorganisms (65.9%). Fifty-five patients (87.3%) died. Mechanical ventilation and underlying renal disease were significant determinants of mortality. In conclusion, Gram-negative bacteria remain the major pathogens in sepsis. The mortality remains very high, and a change in the clinical approach to the septic patient should be employed to improve the outcome.

Which patient is a candidate for empirical therapy against Stenotrophomonas maltophilia bacteraemia? An analysis of associated risk factors in a tertiary care hospital

Stenotrophomonas maltophilia is an emerging nosocomial pathogen with a tendency to be resistant to several antibiotics commonly used to treat nosocomial infections. Early recognition of the risk factors for bacteraemia caused by S. maltophilia could potentially improve the prognosis in these cases. Most data have been obtained from a limited number of descriptive studies. In this retrospective case-control study, we investigated the risk factors for S. maltophilia bacteraemia. We compared cases with 2 different control groups; non-bacteraemic patients and those with bacteraemia caused by Escherichia coli. 37 cases were matched with 37 control patients with nosocomial E. coli bacteraemia and 74 non-bacteraemic patients. The demographic information was extracted from the chart of the patients. When the effects of multiple factors were analysed simultaneously, the presence of a central venous catheter and carbapenem use were associated with an increased risk for bacteraemia caused by S. maltophilia compared with both the non-bacteraemic and bacteraemic control groups. We found a mortality rate of 21.6% in cases vs non-bacteraemic controls; however, this was not a statistically significant difference from that observed in patients with E. coli bacteraemia.

Impact of Initial Antimicrobial Therapy in Patients with Bloodstream Infections Caused by Stenotrophomonas maltophilia

The impact of inappropriate initial antimicrobial therapy on the outcomes of patients with bloodstream infections caused by antibiotic-resistant gram-negative bacilli is not well defined. Recently, in an interesting study by Kang et al., inappropriate initial antimicrobial therapy was found to be associated with an adverse outcome, particularly in patients with a high-risk source of bacteremia caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., and Pseudomonas aeruginosa (1). In addition to the source of bacteremia, presentation with septic shock, P. aeruginosa infection, and an increasing acute physiology, age, and chronic health evaluation (APACHE II) score were poor prognostic factors in this study. Stenotrophomonas maltophilia is an emerging nosocomial pathogen with a tendency to be resistant to several antibiotics commonly used to treat nosocomial infections. Although a recent study reported no significant difference in the outcomes of patients who received appropriate therapy and outcomes of patients who received inappropriate therapy (2), at least two case-controlled studies described inappropriate therapy as an independent risk factor for mortality (3, 4). At our center (Hacettepe University School of Medicine Hospital, a 1,000-bed tertiary-care teaching hospital), we evaluated the factors that influenced the outcomes in patients with bacteremia caused by S. maltophilia. We retrospectively reviewed the reports of our clinical microbiology laboratory to identify the study patients during a six-year period from 1998 to 2004. Case patients were defined as those who were >16 years of age, had at least one blood culture positive for S. maltophilia, and had clinical signs of systemic infection. The mortality rate 30 days after the onset of bacteremia was used as the main outcome measure. Appropriate therapy was defined as one or more agents active against S. maltophilia, given adequate dose and route of administration, not later than 24 h after the blood culture was obtained. All statistical analyses were performed by using SPSS software (version 10.0; SPSS, Chicago, IL). Numerical data were reported (medians and interquartile ranges). To test for the differences between quantitative variables between appropriate and inappropriate therapies, independent-sample t tests were used for normally distributed variables. Differences between categorical variables were analyzed by the chi-square test with the continuity correction or the Fisher exact test where appropriate. Fifty-six patients with S. maltophilia bacteremia were identified. A total of 41 patients were included in the analysis. Fifteen cases whose medical records contained missing data were excluded from the study. The overall 30-day mortality rate was 31.7%. The patients who died within 30 days after the onset of S. maltophilia bacteremia had a longer duration of hospitalization and a higher rate of intensive care unit stay (at the time of initial bacteremia), as well as an increased need for mechanical ventilation and presentation with septic shock (Table ​(Table1).1). Twelve (29.2%) patients had received inappropriate therapy. Eight (66.7%) patients who were treated inappropriately died, compared to 5 (17.2%) of 29 who died though they received an appropriate antibiotic(s). Six of 8 (75.0%) patients who died were on carbapenems when S. maltophilia bacteremia developed. TABLE 1. Demographic characteristics of the patients with bloodstream infection caused by S. maltophilia In this limited study, we have shown a higher mortality rate for the bacteremic patients who did not receive appropriate therapy against S. maltophilia. We believe this issue should be further evaluated by case-controlled studies with a higher number of patients who had similar comorbid factors. In addition, the practicing physician should consider S. maltophilia as the causative organism in a patient who deteriorates under carbapenem therapy.

A cluster of nosocomial Klebsiella oxytoca bloodstream infections in a university hospital.

BACKGROUND On February 19, 2003, four patients (patients 1-4) in the neurology ward underwent cranial magnetic resonance angiography (MRA) and developed fever within 1 hour afterward. Klebsiella oxytoca was isolated from blood cultures of patients 1 through 3. OBJECTIVE To identify the source of this cluster of nosocomial K. oxytoca bloodstream infections. DESIGN Outbreak investigation. SETTING A 1,000-bed university hospital. METHODS The infection control team reviewed patient charts and interviewed nursing staff about the preparation and administration of parenteral fluids. The procedure of cranial MRA was observed. Arbitrarily primed polymerase chain reaction (AP-PCR) was performed to show the clonal relationship among these three strains. RESULTS AP-PCR revealed that three K. oxytoca isolates had the same molecular profile. Cranial MRA was found to be the only common source among these patients. During MRA, before injection of the contrast medium, normal saline solution was infused to check the functioning of the intravenous catheter. Use of the solution for multiple patients was routine, but the access diaphragm of the bottle was not cleansed. The bottle of normal saline solution used on February 19 had already been discarded and the culture sample taken from the solution on the day of observation was sterile. CONCLUSIONS We speculate that normal saline solution became contaminated during manipulation and that successive uses might have been responsible for this cluster. Poor aseptic techniques employed during successive uses appear to be the most likely route of contamination. Use of parenteral solutions for multiple patients was discontinued.