Bloodstream infections (BSI) caused by extended-spectrum ␤-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n ‫؍‬ 104), Klebsiella pneumoniae (n ‫؍‬ 58), or Proteus mirabilis (n ‫؍‬ 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] ‫؍‬ 6.28; 95% confidence interval [CI] ‫؍‬ 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR ‫؍‬ 2.69; 95% CI ‫؍‬ 1.38 to 5.27; P ‫؍‬ 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR ‫؍‬ 2.38; 95% CI ‫؍‬ 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.Bloodstream infections (BSI) caused by organisms that produce extended-spectrum ␤-lactamase (ESBLs) are associated with increased rates of treatment failure and death (1, 14, 15, 19, 22, 25, 28, 30-33, 38, 39, 41, 43, 46, 47, 50, 51). ESBLs are plasmid-mediated beta-lactamases that confer resistance to oxyimino cephalosporins and monobactams (7,33). In most cases, they are the result of mutations involving the classical TEM-1/TEM-2 and SHV-1 type ␤-lactamase genes, although exceptions to this rule (e.g., CTX-M ␤-lactamases) are becoming more and more common (13,27,33,39).Patients at high risk for infection by ESBL-producing organisms are often seriously ill, with histories of lengthy hospital stays and prolonged exposure to invasive medical devices and/or procedures (3,5,13,15,25,35,41,43,49). Prior exposure to antimicrobial therapy is also a well-recognized risk factor for acquisition of an ESBL-producing organism (25,35,43,47).The presence of an ESBL determinant significantly reduces the number of antimicrobial agents to which the infecting organism is susceptible (9). In addition, because of their nosocomial origin and the frequent links between ESBL genes and other resistance genes on the mobile DNA elements that are involved in their dissemination, ESBL producers often present complex multidrug-resistant phenotypes (7,27,33,42).Inade...

Bloodstream infections caused by extended-spectrum-␤-lactamase (ESBL)-producing Klebsiella pneumoniae isolates are a major concern for clinicians, since they markedly increase the rates of treatment failure and death. One hundred forty-seven patients with K. pneumoniae bloodstream infections were identified over a 5-year period (January 1999 to December 2003). The production of ESBLs in bloodstream isolates was evaluated by molecular methods. A retrospective case-case-control study was conducted to identify risk factors for the isolation of ESBLproducing K. pneumoniae or non-ESBL-producing K. pneumoniae isolates in blood cultures. Forty-eight cases infected with ESBL-producing K. pneumoniae isolates and 99 cases infected with non-ESBL-producing K. pneumoniae isolates were compared to controls. Risk factors for isolation of ESBL-producing K. pneumoniae isolates were exposure to antibiotic therapy (odds ratio [OR], 11.81; 95% confidence interval [CI], 2.72 to 51.08), age (OR, 1.14; 95% CI, 1.08 to 1.21), and length of hospitalization (OR, 1.10; 95% CI, 1.04 to 1.16). Independent determinants for isolation of non-ESBL-producing K. pneumoniae were previous urinary tract infection (OR, 8.50; 95% CI, 3.69 to 19.54) and length of hospitalization (OR, 1.07; 95% CI, 1.04 to 1.10). When the initial response was assessed at 72 h after antimicrobial therapy, the treatment failure rate for the ESBL-producing K. pneumoniae-infected group was almost twice as high as that of the non-ESBL-producing K. pneumoniae-infected group (31% versus 17%; OR, 2.19; 95% CI, 0.98 to 4.89). The 21-day mortality rate for all patients was 37% (54 of 147); it was 52% (25 of 48) for patients with ESBL-producing K. pneumoniae bloodstream infections and 29% (29 of 99) for patients with non-ESBLproducing K. pneumoniae bloodstream infections (OR, 2.62; 95% CI, 1.28 to 5.35). In summary, this investigation identifies epidemiological characteristics that distinguish ESBL-producing K. pneumoniae infections from non-ESBL-producing K. pneumoniae ESBL bloodstream infections.

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To evaluate the changing characteristics of HIV-associated bacteremia in the highly active antiretroviral therapy (HAART) era, we conducted a prospective case control study, comparing two periods of time, before (period A) and after (period B) the introduction of HAART. In total, 174 patients with bacteremia and 348 controls were studied. By comparing incidence in periods A and B, a statistically significant reduction of bacteremia, from 11.8 to 6.3/100 person-years (PY), was observed (p = .0001). Incidence of hospital-acquired bacteremia decreased from 5.8 episodes/100 PY in period A to 2.4/100 PY in period B (p = .0005). A similar trend was also observed for community-acquired episodes of bacteremia, with a value close to statistical significance. Logistic regression analysis indicated that intravenous drug abuse, central venous catheter (CVC) use, high value on APACHE III score, and neutropenia were independent risk factors for bacteremia in both the study periods. Interestingly, comparing the prevalence of bacteremia risk factors in the two study periods, we observed a significant reduction in the use of CVC (p = .04, period A versus period B) and in neutropenia (p = .04). The crude mortality rate was 31% in period A and 23% in period B (p = not significant [ns]). Logistic regression analysis indicated that an high value of Acute Physiology and Chronic Health Evaluation III (APACHE III) score (p < .001) predicted an increased risk of death. Analysis of prognostic factors of bacteremia did not significantly differ in both the study periods. We conclude that HAART has determined a significant reduction of the incidence and a modification of the characteristics of bacteremia. This reduced incidence may produce a substantial impact on future morbidity and health care costs of patients with HIV.

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk of HBV reactivation is heightened by the use monoclonal antibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. Emerging data indicate that HBV reactivation could also develop following the use of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is diagnosed, it is mandatory to suspend biologic treatment and start antiviral agents immediately. However, pre-emptive antiviral therapy prior to monoclonal antibody administration is crucial in preventing HBV reactivation and its clinical consequences. Several lines of evidence have shown that risk of HBV reactivation is greatly reduced by the identification of high-risk patients and the use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

HIV-infected children and adolescents present high prevalence of thrombophilic abnormalities. The multivariate model confirmed that high viral replication is independently associated with decrease of protein S and increase of D-dimer, suggesting the advantage of suppressive therapy on coagulation homeostasis and the opportunity of an active control of cardiovascular risk factors starting at a younger age.

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Here, we report a case of a febrile patient with primary bilateral adrenalitis who was successfully treated with an antituberculous regimen Primary isolated tubercular adrenalitis is a very rare clinical entity but it should be considered in cases of fever and enlargement of the adrenal glands Integration of radiological pattern data with epidemiological, clinical and immunological data has high accuracy and specificity, even without histological examinatio