Perioperative Antibiotic Prophylaxis of Wound and Foreign Body Infections: Microbial Factors Affecting Efficacy

Numerous microbial factors are responsible for perioperative infections and influence the efficacy of antibiotic prophylaxis. These factors include the staphylococcal carrier state, bacterial adherence to a number of host proteins, the production of glycocalyx by sessile bacteria, and shifts in antibiotic resistance. A full understanding of the mechanisms involved will lead to further reductions in the number of postoperative infections. Unfortunately, the microbial factors affecting prophylaxis cannot be evaluated separately under clinical conditions; they are easier to study under circumstances whose bacteriologic features are well defined and in which the presence of foreign materials (e.g., sutures) greatly potentiates pathogenic mechanisms. Such circumstances exist, for example, in infections developing after "clean” surgery and in experimental models. Since even clean wounds are found to be contaminated when sampled carefully, the control of infection is more a quantitative than a qualitative problem. The critical period for the development of infection is short: an antibiotic course not exceeding 24 hours seems effective in preventing infectio

Granulocyte Neutral Proteases and Pseudomonas Elastase as Possible Causes of Airway Damage in Patients with Cystic Fibrosis

We studied the possible role of granulocyte neutral proteases as mediators of airway destruction in patients with cystic fibrosis (CF) who were infected with Pseudomonas aeruginosa. We measured the enzymatic activities of bronchial secretions on purified radioactively labeled complement component three (C3), elastin, and a granulocyte elastase-specific substrate. Bronchial secretions from 18 patients with CF who were infected with P aeruginosa had a significantly higher mean value for C3 cleaving, elastolytic, and granulocyte elastase-like activity than did two control groups. High enzymatic activities were observed in patients with CF who have advanced bronchial disease (that had been determined by a clinical scoring system). Kinetics of proteolysis of radioactively labeled C3 and inhibition profiles of the activities of the three enzymatic activities studied suggest that they are mainly derived from granulocytes. In addition, 20 of 31 strains of P aeruginosa isolated from patients with CF inactivated purified α1-antiprotease in vitro. We postulate that granulocyte neutral proteases and P aeruginosa may act synergistically in the airways of patients with CF and may contribute to the destruction of elastin and inactivation of C

Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

A local defense mechanism in bacterial meningitis was evaluated in humans by measuring complement-mediated opsonic activity (CMOA) in normal and infected cerebrospinal fluid (CSF) with a complement-dependent phagocytic bactericidal assay. CMOA was absent in normal untreated CSF and remained undetectable in 20 samples of CSF from patients with viral meningitis and five samples from patients with acute meningococcemia. In contrast, 15 of 27 samples of CSF from patients with acute bacterial meningitis had a measurable CMOA, which was correlated with protein concentrations (P < 0.01) and C4 hemolytic activity (P < 0.001) in the CSF. A favorable outcome of bacterial meningitis was associated with the presence of CMOA in CSF (P < 0.005). Recovery was also correlated with higher levels of C4 (P < 0.01) and C3 (P < 0.05) in CSF and with lower concentrations of microorganisms in the sample of CSF collected at the time of admission (P < 0.01). Thus, CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completel

Foreign Body Infection: Role of Fibronectin as a Ligand for the Adherence of Staphylococcus aureus

Foreign bodies made of polymethylmethacrylate coverslips were implanted subcutaneously into guinea pigs, were explanted four weeks later, and were tested for in vitro adherence of Staphylococcus aureus strain Wood 46. In the presence of serum, the level of staphylococcal adherence to explanted coverslips was 20 times higher than that of adherence to unimplanted coverslips. Adherence to explanted coverslips was caused by fibronectin deposits on the foreign body surface and was inhibited in a dose-related fashion by specific antibodies to fibronecti

Host Factors Selectively Increase Staphylococcal Adherence on Inserted Catheters: A Role for Fibronectin and Fibrinogen or Fibrin

Intravascular catheters are prone to staphylococcal infections. To study the role in staphylococcal adherence played by fibrinogen or fibrin and fibronectin deposited on inserted catheters, 187 peripheral or central cannulae were prospectively removed from hospitalized patients. Compared with uninserted catheters, which allowed only minimal adherence, previously inserted catheters promoted significant adherence of staphylococcal isolates from patients with intravenous device infections. Adhesion-promoting properties were studied with laboratory strains having well-defined affinities for either fibronectin or fibrinogen adherence of Staphylococcus aureus Cowan I, which has the highest affinity for both adhesins, was more strongly promoted (10- to 50-fold) on inserted cannulae than was that of S. aureus Wood 46 (4- to lO-fold) or Staphylococcus epidermidis Rp 12 (2.2-fold), which has no affinity for fibrinogen but does for fibronectin. Although all types of cannulae contained significant amounts of fibrin, which may promote adherence of coagulase-positive staphylococci, results obtained with coagulase-negative isolates suggested that in vivo-deposited fibronectin is also a critical determinant in this proces