No abstract

c Gram-negative bacteremia is highly fatal, and hospitalizations due to sepsis have been increasing worldwide. Molecular tests that supplement Gram stain results from positive blood cultures provide specific organism information to potentially guide therapy, but more clinical data on their real-world impact are still needed. We retrospectively reviewed cases of Gram-negative bacteremia in hospitalized patients over a 6-month period before (n ‫؍‬ 98) and over a 6-month period after (n ‫؍‬ 97) the implementation of a microarray-based early identification and resistance marker detection system (Verigene BC-GN; Nanosphere) while antimicrobial stewardship practices remained constant. Patient demographics, time to organism identification, time to effective antimicrobial therapy, and other key clinical parameters were compared. The two groups did not differ statistically with regard to comorbid conditions, sources of bacteremia, or numbers of intensive care unit (ICU) admissions, active use of immunosuppressive therapy, neutropenia, or bacteremia due to multidrug-resistant organisms. The BC-GN panel yielded an identification in 87% of Gram-negative cultures and was accurate in 95/97 (98%) of the cases compared to results using conventional culture. Organism identifications were achieved more quickly post-microarray implementation (mean, 10.9 h versus 37.9 h; P < 0.001). Length of ICU stay, 30-day mortality, and mortality associated with multidrug-resistant organisms were significantly lower in the postintervention group (P < 0.05). More rapid implementation of effective therapy was statistically significant for postintervention cases of extended-spectrum beta-lactamase-producing organisms (P ‫؍‬ 0.049) but not overall (P ‫؍‬ 0.12). The Verigene BC-GN assay is a valuable addition for the early identification of Gram-negative organisms that cause bloodstream infections and can significantly impact patient care, particularly when resistance markers are detected. Bloodstream infection remains one of the deadliest and costliest conditions in the United States, more than doubling between 2000 and 2008 and becoming the sixth most common reason for hospitalization (1). Gram-negative bacteremia has become an ever more pressing public health concern, as numbers across the globe continue to rise (2, 3). Although Gram-negative organisms are only responsible for ϳ30% of cases of hospitalacquired infections, they account for 70% of such cases in intensive care units (ICU) in the United States (4). These organisms, including multidrug-resistant (MDR) Pseudomonas aeruginosa and extended-spectrum beta-lactamase (ESBL) or carbapenemresistant Enterobacteriaceae (CRE), are associated with higher mortality rates (1, 3, 4).A timely and appropriate antimicrobial therapy selection is of particular importance. Delays in effective therapy and ineffective empirical therapy are associated with increased patient mortality (4-7). Growing evidence suggests that appropriate, early antibiotic therapy can improve patient outcomes (3,4,6,8). New rapid m...

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clonesequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age <40 years) and currently comprises a quarter of fluoroquinolone-resistant clinical E. coli urine isolates.

Honey has been used as a traditional remedy for skin and soft tissue infections due to its ability to promote wound healing. Manuka honey is recognized for its unusually abundant content of the antibacterial compound, methylglyoxal (MGO). The Unique Manuka Factor (UMF) grading system reflects the MGO concentration in Manuka honey sold commercially. Our objective was to observe if UMF values correlated with the antibacterial activity of Manuka honey against a variety of pathogens purchased over the counter. The antibacterial effect of Manuka honey with UMF values of 5+, 10+, and 15+ from the same manufacturer was assessed by the broth microdilution method. Minimum inhibitory concentration (MIC) values were determined against 128 isolates from wound cultures representing gram-positive, gram-negative, drug-susceptible, and multi-drug resistant (MDR) organisms. Lower MICs were observed with UMF 5+ honey for staphylococci (n = 73, including 25 methicillin-resistant S. aureus) and Pseudomonas aeruginosa (n = 22, including 10 MDR) compared to UMF 10+ honey (p<0.05) and with UMF 10+ compared to UMF 15+ (p = 0.01). For Enterobacteriaceae (n = 33, including 14 MDR), MIC values were significantly lower for UMF 5+ or UMF 10+ compared to UMF 15+ honey (p<0.01). MIC50 for UMF 5+, UMF 10+, and UMF 15+ honey against staphylococci was 6%, 7%, and 15%, and for Enterobacteriaceae was 21%, 21%, and 27%, respectively. For Pseudomonas aeruginosa MIC50 was 21% and MIC90 was 21–27% for all UMFs. Manuka honey exhibited antimicrobial activity against a spectrum of organisms including those with multi-drug resistance, with more potent activity overall against gram-positive than gram-negative bacteria. Manuka honey with lower UMF values, in our limited sampling, paradoxically demonstrated increased antimicrobial activity among the limited samples tested, presumably due to changes in MGO content of honey over time. The UMF value by itself may not be a reliable indicator of antibacterial effect.

Sustained elevation of interleukin-10/tissue necrosis factor ratio at 72 hours suggests a dysregulated immune response and may be used to guide management to improve outcomes.