Rapid molecular determination of methicillin resistance in staphylococcal bacteraemia improves early targeted antibiotic prescribing: a randomized clinical trial.

Empiric therapy of methicillin-susceptible Staphylococcus aureus (MSSA) infections with vancomycin is associated with poorer outcome than targeted therapy with ß-lactams. Our objective was to evaluate whether rapid determination of methicillin resistance shortens the time from Gram stain to targeted antimicrobial therapy in staphylococcal bacteraemia, thereby reducing vancomycin overuse. This was a single-centre open parallel RCT. Gram-positive cocci in clusters in positive blood culture underwent real-time PCR for rapid species and methicillin resistance determination parallel to conventional microbiology. Patients were randomized 1:1 so that clinicians would be informed of PCR results (intervention group) or not (control group). Eighty-nine patients (intervention 48, control 41) were analysed. MRSA was identified in seven patients, MSSA in 46, and CoNS in 36. PCR results were highly concordant (87/89) with standard microbiology. Median time (hours) from Gram stain to transmission of methicillin-susceptibility was 3.9 (2.8-4.3) vs. 25.4 (24.4-26-7) in intervention vs. control groups (p <0.001). Median time (hours) from Gram stain to targeted treatment was similar for 'all staphylococci' [6 (3.8-10) vs. 8 (1-36) p 0.13] but shorter in the intervention group when considering S. aureus only [5 (3-7) vs. 25.5 (3.8-54) p <0.001]. When standard susceptibility testing was complete, 41/48 (85.4%) patients in the intervention group were already receiving targeted therapy compared with 23/41 (56.1%) in the control group (p 0.004). There was no significant effect on clinical outcomes. Rapid determination of methicillin resistance in staphylococcal bacteraemia is accurate and reduces significantly the time to targeted antibiotic therapy in the subgroup of S. aureus, thereby avoiding unnecessary exposure to vancomycin.

Doxycycline vs. macrolides in combination therapy for treatment of community-acquired pneumonia.

We assessed the comparative efficacy of empirical therapy with beta-lactam plus macrolide vs. beta-lactam plus doxycycline for the treatment of community-acquired pneumonia (CAP) among patients in the Australian Community-Acquired Pneumonia Study. Both regimens demonstrated similar outcomes against CAP due to either 'atypical' (Chlamydophila, Legionella or Mycoplasma spp.) or typical bacterial pathogens.

Comparison of the bacterial isolates and antibiotic resistance patterns of elderly nursing home and general community patients.

BACKGROUND: Nursing home-acquired infections may differ from general community-acquired infections in bacteriology and antibiotic resistance. However, there are currently limited data on this topic in the Australian setting. AIMS: To compare bacterial isolates and antibiotic resistance patterns, from pathology specimens of nursing home and community patients, and to comment on the suitability of empiric antibiotic guidelines for nursing home-acquired infection. METHODS: This was a retrospective cohort study of patients, aged ≥ 65 years, who resided in either nursing homes or the general community. Patients with a hospital admission in the previous 28 days were excluded. Positive specimen cultures, collected between July 2003 and June 2008 in the Emergency Department and Outpatient Clinics of the Austin Hospital (Melbourne), were examined. The main outcome measures were the bacterial isolates, and their antibiotic resistance patterns, of patients from nursing homes and the general community. RESULTS: Specimens of blood (638), sputum (425), urine (4044) and wound cultures (785) were examined. The bacteriology of blood culture isolates did not differ between the two groups (P= 0.3). However, the bacteriology of sputum, urine and wound cultures differed significantly between the groups (P= 0.025, P < 0.001, P= 0.004 respectively). There were also higher proportions of antibiotic resistance among some bacteria in nursing home patients, especially methicillin resistance among Staphylococcus aureus isolates across all specimen types, and resistance to several empiric antibiotics among Enterobacteriaceae isolates in urine cultures. CONCLUSION: Empiric antibiotic guidelines appear adequate to treat nursing home-acquired septicaemia and pneumonia. However, guidelines for urinary tract infections and wound infections may need to be refined.

Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency.

BACKGROUND: . Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G(2) (IgG(2)) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection. METHODS: Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women. RESULTS: Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P < .001), anemia (P < .001), and low levels of total IgG (P= .01), IgG(1) (P= .022), and IgG(2) (15 of 19 vs 5 of 20; P= .001; mean value +/- standard deviation [SD], 1.8 +/- 1.7 g/L vs 3.4 +/- 1.4 g/L; P= .003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P= .02) and low mean IgG(2) levels (P= .043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG(2)-deficient patients at a mean (+/- SD) of 90 +/- 23 days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG(2) deficient. Among 17 healthy pregnant control subjects, mildly low IgG(1) and/or IgG(2) levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG(2) (P= .001). CONCLUSIONS: Severe H1N1 infection is associated with IgG(2) deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG(2) level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG(2) deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.

Low-level vancomycin resistance in Staphylococcus aureus--an Australian perspective.

Low-level vancomycin resistance in Staphylococcus aureus has emerged as a clinical problem over the past 8 years. The clinical relevance of this resistance has been questioned, and laboratory detection remains difficult and time consuming. There is, however, increasing evidence linking low-level vancomycin resistance with glycopeptide treatment failure in serious Staphylococcus aureus infections. Diagnostic laboratories and clinicians need to be aware of this resistance phenotype, to have procedures in place to detect the resistance, and to have strategies for managing patients with infections caused by resistant strains.

Characterization of renal Na-K-ATPase gene expression by in situ hybridization.

Na-K-ATPase is a heterodimer of alpha- and beta-subunits often referred to as the 'sodium pump' responsible for the maintenance of cell volume and electric potential across cell membranes. In the present study we have used antisense RNA probes to localize these subunits in the rat kidney by in situ hybridization. alpha 1-Subunit and beta-subunit gene expression are highest in cortical distal convoluted tubules, and the thick ascending limb of the loops of Henle; high in some proximal convoluted tubules, and low in the collecting ducts and blood vessels. Expression of the alpha 11 and alpha 111 isoforms is very low or absent throughout the kidney. These results confirm and extend studies of Na-K-ATPase enzyme activity levels and immunocytochemical localization in the kidney.