Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus

Staphylococcus aureus is a significant infectious threat to global public health. Acquisition or synthesis of heme is required for S. aureus to capture energy through respiration, but an excess of this critical cofactor is toxic to bacteria. S. aureus employs the heme sensor system (HssRS) to overcome heme toxicity; however, the mechanism of heme sensing is not defined. Here, we describe the identification of a small molecule activator of HssRS that induces endogenous heme biosynthesis by perturbing central metabolism. This molecule is toxic to fermenting S. aureus, including clinically relevant small colony variants. The utility of targeting fermenting bacteria is exemplified by the fact that this compound prevents the emergence of antibiotic resistance, enhances phagocyte killing, and reduces S. aureus pathogenesis. Not only is this small molecule a powerful tool for studying bacterial heme biosynthesis and central metabolism; it also establishes targeting of fermentation as a viable antibacterial strategy

Risk Factors For Wound Infections After Implant Surgery

OBJECTIVE: Post-operative wound infection (POWI) rates for implant surgery are in the range of 0.08 to 13% in spite of the many advances in surgery in the past decades. It is therefore imperative that we develop a system of predicting the occurrence of POWI as a key to effective prevention. One approach is for each hospital to identify its own risk factors as predictors of POWI. This is one of such studies. DESIGN: A controlled prospective study between August 1998 and July 2000. METHODS: Over 24 months, patients who had open reduction and internal fixation (ORIF) with implants were recruited based on strict inclusion criteria. POWI was diagnosed using the National Research Council Criteria as presence of pus in a wound. Patients who had bone surgery without implants formed the control. Risk factors were explored using both univariate and multivariate analysis. RESULTS: There were 289 patients admitted into study comprising 219 in the test and 70 in the control groups. Twelve of these developed POWI corresponding to an infection rate of 5.5%. Of the eleven potential risk factors tested, pre-operative hospitalization, ward of admission, theatre suit, theatre population and duration of surgery were found to have a statistically significant association with the development of POWI. CONCLUSION: Outpatient pre-operative work-up in elective cases, reduction in operative time within safety limits and strict theatre asepsis will form veritable approaches to reducing our wound infection rates Nig Jnl Orthopaedics & Trauma Vol.2(2) 2003: 101-10