Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study.

BACKGROUND: Patients with neutropenic fever after 4-7 days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment. METHODS: Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the 'preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the 'empirical' arm received CAV in accordance with established guidelines. RESULTS: Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm. CONCLUSIONS: A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.

Attitudes of patients, visitors and healthcare workers at a tertiary hospital towards influenza A (H1N1) response measures.

INTRODUCTION: We sought to determine the opinions of patients, their visitors and healthcare workers regarding Influenza A (H1N1) response measures instituted within a tertiary hospital in Singapore. MATERIALS AND METHODS: This questionnaire study was undertaken from 21 May 2009 to 31 August 2009. RESULTS: There were 92 respondents, ranging in age from 15 to 77 years. Of the 90 who identified their role, 35.6% were patients, 12.2% visitors and 52.2% health care professionals. About 23% of respondents disagreed that one could have H1N1 without fever or fl u-like symptoms, while 14.3% thought influenza could not be caught from an asymptomatic infected person. About 30% perceived the H1N1 death rate as high. From this study, 82.2% of respondents agreed or strongly agreed that Singapore's H1N1 responses were essential, while 14.6% found it overdone. In particular, healthcare workers and doctors found their professional work to be inconvenienced. Although more than two-thirds of doctors held this view, an equal proportion agreed the outbreak response was essential. CONCLUSIONS: There was a high level of acceptance of response measures as essential, despite the perceived inconvenience. We propose that the success of containment measures requires unity of purpose and understanding among stakeholders at all levels.

Active surveillance testing and decontamination strategies in intensive care units to reduce methicillin-resistant Staphylococcus aureus infections.

BACKGROUND: Active surveillance testing (AST) and decontamination strategies (DS) using a topical methicillin-resistant Staphylococcus aureus (MRSA) cleansing agent was introduced in July 2007 in a medical intensive care unit (MICU) and a surgical ICU (SICU) of a tertiary care hospital to reduce the incidence of MRSA infection. METHODS: Data on ICU admissions between July 1, 2007, and June 30, 2008, was analyzed. All subjects, excluding known MRSA status, had an ICU length of stay (LOS) of more than 24 hours and nasal swabs performed on ICU admission, every 7 days during the ICU stay, and on discharge. MICU and SICU specimens were sent for culture and in-house real-time polymerase chain reaction, respectively. MRSA-colonized (MRSAc) patients were subjected to contact isolation precautions and DS for 5 days or until ICU discharge. Data recorded included demographics, LOS, and antibiotic use. Results were analyzed using SPSS. Control charts were used to determine special cause variation. RESULTS: Of 653 eligible patients admitted to the ICU, 85 (13%) were determined to be MRSAc on ICU admission. A further 15% (52 of 351) were determined to be MRSAc during the ICU stay or at discharge. Thus, AST detected MRSA in at least 137 of the 653 patients (21.0%). In contrast, clinical cultures for MRSA were positive in only 12 patients (1.8%). Compared with noncolonized patients, MRSAc patients at any screening point had a longer pre-ICU LOS (P =.001), received more antibiotics (P = .004), and had a longer ICU LOS (P = .003). Compared with the preintervention period of July 2006 to June 2007, there was no significant reduction in mean MRSA infection incidence rate in both ICUs (3.8 to 3.0 per 1000 patient-days [P = .057] in the SICU and 1.4 to 1.7 per 1000 patient-days in the MICU) following intervention. CONCLUSIONS: In ICUs, AST detected 11 times more MRSA than clinical cultures. The lack of reduction in MRSA infection rates in the ICUs does not negate the roles of AST and DS, but does argue for better study design and outcome measures like MRSA transmission incidence, which perhaps would have demonstrated a true benefit of AST and DS.

Evolving EMRSA-15 epidemic in Singapore hospitals.

The aim of this study was to determine the extent of EMRSA-15 spread in hospitals in Singapore. Molecular analysis of 197 non-duplicate meticillin-resistant Staphylococcus aureus (MRSA) isolates collected from five acute care public hospitals in Singapore in May 2005 revealed that 66 (33.5%) were EMRSA-15 while 121 (61.4%) belonged to the endemic multidrug-resistant ST239 clone. Median and mode vancomycin MIC for both major clones of health-care-associated MRSA were relatively high at 2.0 microg ml-1. Subsequent laboratory surveillance data collected from the first half of 2006 confirmed increasing numbers of the EMRSA-15 clone--ranging from 25.0 to 66.1% of all MRSA isolated in local hospitals--replacing the ST239 clone island-wide.

EMRSA-15 Bacteremia is not Associated with a Worse Outcome Compared with Bacteremia Caused by Multidrug-Resistant MRSA.

EMRSA-15 (ST22-MRSA-IV) is rapidly replacing the endemic ST239 health care-associated methicillin-resistant Staphylococcus aureus clone in Singapore. A one-year single-centre cohort study of inpatients with MRSA bacteremia was performed to determine if bacteremia caused by EMRSA-15 was associated with worse outcomes compared to bacteremia caused by the endemic ST239 strain. Strains were identified by antibiotypes, and subsequent validation was performed on a selected sample of MRSA strains via pulsed-field gel electrophoresis and staphylococcal chromosome cassette mec typing. Two hundred and twenty-eight patients with MRSA bacteremia were studied; Seventy-three were infected with EMRSA-15. EMRSA-15 and ST239-infected patients were similar regarding gender, frequencies of most co-morbidities, and risk factors for adverse outcomes. Similar numbers of EMRSA-15-infected and ST239-infected patients died (24.7% vs 27.1%, P=0.70) or developed complicated infections (41.1% vs 40.0%, P=0.88). After multivariate analysis, EMRSA-15 as a cause of bacteremia was not significantly associated with either death or development of complicated infections, although inappropriate therapy (5.45-fold, P<0.01) and a respiratory source of bacteremia (4.69, P<0.01) were independently associated with subsequent mortality. The increased propensity of EMRSA-15 for dissemination was not associated with increased virulence in our patients. Further work in determining the mechanisms by which highly transmissible MRSA spreads rapidly is required to better target infection control approaches at these important emerging MRSA clones.

Establishment of ST30 as the predominant clonal type among community-associated methicillin-resistant Staphylococcus aureus isolates in Singapore.

The number of infections attributable to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Singapore is progressively increasing. Most cases in the past 2 years were caused by Panton-Valentine leukocidin-positive isolates belonging to sequence type 30, according to multilocus sequence typing. This has clearly become the predominant sequence type among CA-MRSA isolates in Singapore.