Use of Quinolones for the Treatment of Osteomyelitis and Septic Arthritis

The low minimal inhibitory concentrations and minimal bactericidal concentrations of the quinolones for most pathogenic gram-negative and many gram-positive organisms, the ease of their administration, and their good oral absorption make them good candidates for the treatment of chronic bone infections. Data presently available suggest that the quinolones are effective in the treatment of experimental osteomyelitis due to Pseudomonas aeruginosa, osteomyelitis due to other gram-negative organisms, and (when combined with rifampin) in the treatment of gram-positive osteomyelitides. Quinolones have also been shown to be effective in the treatment of experimental septic arthritis. These results were confirmed by clinical studies. Quinolones have been effective in the treatment of patients with gram-negative bacterial bone infections and have been as effective as conventional antistaphylococcal therapy in the treatment of osteomyelitis due to Staphylococcus aureus. Finally, it should be kept in mind that as yet quinolones have not been released for use as therapy for childhood infection

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

Resistance of Staphylococcus aureus Recovered from Infected Foreign Body In Vivo to Killing by Antimicrobials

Because persistence of infections associated with prosthetic material despite the use of appropriate antibioticsis a major clinical problem,the antimicrobial susceptibility of bacteria responsible for a chronic subcutaneous tissue cage infection in rat was investigated ex vivo. Three to 6 weeks after the initiation of infection, suspensions of two strains of Staphylococcus aureus recovered from the foreign body surface and surrounding fluid wereexposed to either oxacillin, vancomycin, fleroxacin, gentamicin, or rifampin. The MBCs of these bacteria were markedly elevated, in most cases 128 to >256 times higher than the MBCof batch culture S. aureus in either logarithmic or stationary phase. Kinetic studies showed the bacteria did not growwhen incubated for 2 h in Mueller-Hinton broth, possibly reflecting dormancy. Their killing wasslow and incompleteby all antibioticsat > 8 times their MIC. These data provide direct evidence of a decreased susceptibility of S. aureus to the killing effect of antimicrobials during chronic foreign body infections in viv

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

Contribution of Tumor Necrosis Factor to Host Defense against Staphylococci in a Guinea Pig Model of Foreign Body Infections

The contribution of the cytokine tumor necrosis factor (cachectin; TNF) to host defenses against staphylococcal foreign body infections was studied in vivo. In tissue cages subcutaneously implanted into guinea pigs, progressive infection was initiated by a very low inoculum (100 cfu) of Staphylococcus aureus with a success rate of 100%, as is frequently encountered in related clinical situations. Locally injected autologous bacterial components derived from the cell wall of S. aureus, in particular peptidoglycan, were very active in raising TNF levels in tissue cage fluid and in preventing the development of infection by the 100% infective dose of the test strain. Furthermore, injection of murine recombinant TNF into tissue cages could substitute for the bacterial components in preventing experimental infection by S. aureus. The protective effect of TNF-eliciting bacterial components could be neutralized by anti-TNF antibodies. A local increase in TNF levels might improve host defenses against staphylococcal foreign body infection