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Gram-negative resistance is an increasingly important consideration when initiating empiric antimicrobial therapy in intensive care units. Infection with a resistant organism has been associated with increased morbidity and mortality as [...]

Background: High doses of chemotherapy in patients who undergo autologous hematopoietic stem-cell transplantation (HSCT) can result in delayed or incomplete engraftment. Granulocyte colony-stimulating factors are used to decrease the time to engraftment; however, the optimal timing of filgrastim initiation following autologous HSCT is unknown. Objective: This retrospective study at a single institution compared neutropenia recovery of patients who received filgrastim on day +5 after autologous HSCT versus those who received it on day +10. Methods: Patients were included if they began receiving filgrastim on day +5 (±1) or day +10 (±1) after autologous HSCT. Patients were matched based on age and type of malignancy. The primary end point was time to engraftment. Secondary end points included length of hospital stay, rates of infection, and total febrile days. Results: Data were collected for 158 patients. Time to engraftment was faster in patients who began receiving filgrastim on day +5 than in patients who began receiving filgrastim on day 5 +10 (8.27 days vs 8.96 days; P = .006). The average number of doses per patient differed significantly: 7 for day +5 recipients and 3 for day +10 recipients (P <.01). No significant differences were observed in the length of hospital stay, rates of infection, or total febrile days. Conclusion: The authors believe that the difference in engraftment time between the study groups is not clinically meaningful, because secondary end points were similar in these groups. Results indicate that initiating filgrastim on day +10 following autologous HSCT would be safe and economical. [ABSTRACT FROM AUTHOR]

Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/ dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections. [ABSTRACT FROM AUTHOR]

Purpose: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS.Patients/Methods: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS.Results: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer’s dosing recommendation.Conclusions: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients. [ABSTRACT FROM PUBLISHER]

We used the time-kill methods to determine the presence, or lack of antagonism resulting from the combination of voriconazole and amphotericin B against several fluconazole susceptible and resistant Candida isolates. The drug combination was tested both sequentially and concurrently, by the means of a pre-exposure period to voriconazole. No antagonism was found to result from simultaneous exposure to voriconazole and amphotericin B. However, marked antagonism was found in all tested isolates after pre-exposure to voriconazole, followed by concurrent exposure to both agents. Furthermore, isolates susceptible to fluconazole also displayed antagonism of amphotericin B following pre-exposure to voriconazole followed by azole removal and introduction of amphotericin B alone. These data provide further evidence that concurrent use of azole amphotericin B combination therapy against Candida species should be discouraged. Additionally, the persistence of antagonism following the removal of voriconazole, suggests that physiochemical differences among the azoles significantly affects the expression of antagonism. [ABSTRACT FROM PUBLISHER]

Background: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms are becoming increasingly common and present significant challenges in terms of treatment. Carbapenems is the antibiotic class of choice for treatment of these types of infections. Ertapenem is the newest carbapenem, capable of being dosed once daily, and has some in vitro but little in vivo evidence supporting its use for the treatment of these resistant infections., Objective: To examine the clinical and microbiologic outcomes associated with ertapenem therapy of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis infections., Methods: This was a retrospective case series that examined the clinical and microbiologic outcomes of 22 patients who received ertapenem for treatment of an ESBL infection at Rush University Medical Center in Chicago, IL, during 2003-2005., Results: The majority (16/22) of patients received ertapenem for consolidation rather than initial therapy. Different antibiotics most commonly used were other carbapenems, piperacillin/tazobactam, and aminoglycosides. The most common infections treated were lower urinary tract infections and osteomyelitis. Clinical efficacy was determined in all 22 patients, with 20 (91%) patients having a positive outcome, defined as either clinical improvement or clinical cure. The best clinical cure rate was seen with wound infections, where all 3 patients examined were found to be clinically cured. Microbiologic efficacy was determined in 7 patients, with 6 (85.7%) defined as microbiologic cure. One patient was found to be both a clinical and microbiologic failure and was also found to have developed an ertapenem-resistant strain of E. coli., Conclusions: These results demonstrate potential microbiologic and clinical efficacy of ertapenem for treatment of ESBL-producing infections and the need for a prospective, randomized study examining its efficacy versus that of other carbapenems.