In-vitro activity of temafloxacin for Gram-positive pathogens

The antimicrobial activity of tcmafioxacin against aerobic Gram-positive cocci was compared to that of ciprofloxacin, ofloxacin, fleroxacin and pefloxacin using the broth microdilution technique. Temafloxacin was mom active than the other four fluoroquinolones, particularly for viridans streptococci and Streptococcus pneumoniaeniae. The MIC90 of temafloxacin was at least four-fold lower than that of ciprofloxacin and ofloxacin for viridans strtptococci and penicillin-susceptible pneumococci. The MIC50s and MIC90s of temafloxacin were equal to or lower than those of the other fluoroquinolones for rnethicillin-susceptible Staphylococnu aureus (MSSA), methicillin-resistant S.aureus (MRSA), and methicillin-susceptible and methicillin-resistant coagulasc-negative staphylococci Temafloxadn was more active against all the other Gram-positive aerobes (except Enterococcus faecalis) tested than the other fluorquinolone

Protection Against Chronic Pyelonephritis in Rats by Suppression of Acute Suppuration: Effect of Colchicine and Neutropenia

Previous experiments in rats have suggested that renal scarring after acute, obstructive pyelonephritis due to Escherichia coli results from parenchymal damage due to acute inflammation and suppuration. To assess the role of acute infiltration by polymorphonuclear leukocytes (PMNLs) in the pathogenesis of chronic pyelonephritis (CPN), rats were either treated with colchicine to depress leukcoyte motility or rendered neutropenic with a single dose of cyclophosphamide. Colchicine given during acute pyelonephritis reduced kidney inflammation and protected against CPN two months later. Similarly, neutropenia reduced acute inflammation and protected against chronic parenchymal destruction and scarring. Protection against renal scarring in both colchicine-treated and neutropenic rats occurred despite higher renal bacterial counts during acute pyelonephritis. These experiments provide further evidence that CPN (renal scarring) results from kidney damage that occurs during early acute obstructive pyelonephritis. This damage appears to result from infiltration of the kidney by PMNLs rather than direct damage from bacterial infectio

Role of Complement-Derived and Bacterial Formylpeptide Chemotactic Factors in the In Vivo Migration of Neutrophils in Experimental Escherichia coli Pyelonephritis in Rats

In experimental Escherichia coli pyelonephritis, the bacterial multiplication in the kidney parenchyma triggers a burst of neutrophil extravascular migration, as measured by the myeloperoxidase (MPO) activity in the kidney, a marker for tissue neutrophil infiltration. To test the mechanisms of in vivo neutrophil migration, pyelonephritis was surgically induced in rats that were then either complement-depleted with cobra venom factor (CVF), resulting in a profound hypocomplementemia for 72 h after inoculation, or treated with phenylbutazone (PB), a competitive antagonist of bacterial chemotactic formylpeptides. Compared to controls, CVF-and PB-treated animals killed when the neutrophil infiltration started (32 h) had a significantly reduced neutrophil infiltration, as measured by kidney MPO activity. This effect disappeared in animals killed 72 h after surgery, when neutrophil infiltration peaked. These data suggest that redundant chemotactic mechanisms triggered neutrophil migration. Inhibiting one of these mechanisms only transiently delayed neutrophil migration but did not affect the peak infiltratio

Failure of Dexamethasone to Prevent Polymorphonuclear Leukocyte Infiltration During Experimental Acute Exudative Pyelonephritis and to Reduce Subsequent Chronic Scarring

In experimental acute exudative pyelonephritis (AEP), a role for polymorphonuclear leukocyte (PMNL) infiltration in the pathogenesis of kidney scarring has been suggested indirectly. To directly quantitate PMNL infiltration during AEP, we developed an assay for measuring the content in the kidney of myeloperoxidase (MPO), an enzyme present in PMNLs and absent in kidney tissue. This assay was a specific and sensitive marker of the kidney PMNL content. We used this assay to measure in rats with AEP the effect of dexamethasone, administered in an attempt to mitigate the acute inflammatory response. Compared with saline, dexamethasone given during AEP strikingly reduced kidney swelling, measured by the kidney-weight increase, but failed to reduce PMNL infiltration, measured by the kidney MPO content. Despite reduced kidney swelling during AEP, dexamethasone treatment failed to prevent subsequent kidney scarring, an observation indicating that PMNLs playa role in the development of permanent kidney damage during AE

An Epidemic of Food-Borne Listeriosis in Western Switzerland: Description of 57 Cases Involving Adults

This article describes 57 cases of listeriosis that occurred in adults in western Switzerland during an outbreak associated with the consumption of a soft cheese. Twenty-one percent of the cases were of bacteremia, 40% were of meningitis, and 39% were of meningoencephalitis. Overall, 42% of the patients had an underlying disease and 54% were >65 years of age. Patients with bacteremia were significantly older than those with meningitis or meningoencephalitis (median ages, 75, 69, and 55 years, respectively). The epidemic strain, defined by phage typing, was isolated in three-quarters of the listerial cases observed during the epidemic period and did not appear to differ significantly from the nonepidemic strains in terms of virulence. The overall mortality associated with the 57 cases was 32%. Among the patients' characteristics, age and type of clinical presentation were independent predictors of death in a multivariate logistic regression model (pseudo-r2 [coefficient of determination], .26; both P values <.05), and a presentation of meningoencephalitis was associated with an increased death risk (odds ratio, 6.5; 95% confidence interval, 1.1-39.5; P < .05). Neurological sequelae developed in 30% of the survivors of CNS listeriosi

Experimental Bacterial Endocarditis After Dental Extractions in Rats with Periodontitis

The development of bacterial endocarditis was analyzed after dental extractions in rats with or without periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars and placing the animals on a high sucrose diet for 14 weeks. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hr later the maxillary first molars were extracted. The animals were killed 72 hr after the extractions. In rats with periodontal disease, extractions resulted in a 48% (14 of 29) incidence of bacterial endocarditis, most cases of which were due to Streptococcus spp. (one was caused by Staphylococcus aureus). In contrast, when the teeth with a healthy periodontium were extracted, only 6% (one of 15) of the rats developed endocarditis. When catheters were placed in anim, tis with periodontal disease but no extractions were performed, no endocarditis occurre

Use of Immunoglobulins in Prevention and Treatment of Infection in Critically III Patients: Review and Critique

The study of the use of standard intravenous immunoglobulin (IVIG) preparations as adjunctive therapy for seriously ill patients is motivated bythe need to restore immunoglobulin G depleted because of trauma or surgery and/or by the need to provide patients with specific antibodies to various microorganisms. Whereas no clinical studies have shown that standard IVIG has therapeutic efficacy, some data suggest that its prophylactic use is beneficial. Antisera or IVIG prepared from individuals who are hyperimmunized with the biologically active, highly conserved core portion of the endotoxin of gram-negative bacteria confer variable degrees of protection in animal models and clinical trials. Two clinical trials with use of monoclonal antibodies to core lipopolysaccharide have been completed. Only subsets of patients with gram-negative sepsis were protected by the monoclonal antibodies, but the results of the studies were discrepant in regard to the specific characteristics of patients who benefited from the administration ofthese antibodies. Further studies will be necessary to establish whether this therapy can be recommended for critically ill patient

Treatment of Gram-Negative Septic Shock with Human IgG Antibody to Escherichia coli J5: A Prospective, Double-Blind, Randomized Trial

In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli 15 (J5-IVIG) with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock. At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either J5-IVIG or IVIG. Of the 100 patients randomized, 71 (30 receiving J5-IVIG and 41 receiving IVIG) had a documented gram-negative infection. Mortality from gram-negative septic shock was 50% (15 of 30) in J5-IVIG recipients and 49% (20 of 41) in IVIG recipients. In addition, treatment with J5-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock. Thus we conclude that 15-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shoc