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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 127 records · Page 7Linked to original sources
PubMed1985

Activities of pefloxacin and ciprofloxacin in experimentally induced Pseudomonas pneumonia in neutropenic guinea pigs.

Pefloxacin and ciprofloxacin are two new quinoline carboxylic acid derivatives that have activity in vitro against a wide range of gram-negative bacteria, including Pseudomonas aeruginosa. Using a well-standardized model of Pseudomonas pneumonia in neutropenic guinea pigs, we tested the efficacy in vivo of these new agents. Both were highly effective in increasing survival and decreasing bacterial counts in the lungs of surviving animals. Pefloxacin and ciprofloxacin were significantly better (P less than 0.05) than aminoglycosides or beta-lactams tested in prior studies with this model, and they were as effective as combination therapy with aminoglycosides and beta-lactams. Resistance to either ciprofloxacin or pefloxacin did not emerge during the study period. Further studies with these drugs in the therapy of Pseudomonas sp. infections are warranted.

Agranulocytosis↗
PubMed1985

Pefloxacin therapy for experimental endocarditis caused by methicillin-susceptible or methicillin-resistant strains of Staphylococcus aureus.

The therapeutic efficacy of pefloxacin in experimental endocarditis caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus was evaluated. In rabbits infected with a methicillin-susceptible strain, 4 days of pefloxacin therapy significantly reduced both the number of bacteria per gram of vegetation and the mortality rate compared with untreated controls, and pefloxacin was equivalent to cephalothin. Pefloxacin was also as effective as vancomycin in reducing vegetation titers and mortality rate in animals with endocarditis caused by a methicillin-resistant strain. These results suggest that pefloxacin may be an effective agent in the therapy of serious infections caused by either methicillin-susceptible or -resistant strains of S. aureus.

Animals↗
PubMed1985

Comparison of ceftriaxone and ampicillin plus chloramphenicol for the therapy of acute bacterial meningitis.

Ceftriaxone, a new third-generation cephalosporin, appears to be promising for the therapy of acute bacterial meningitis. The 90% MBCs of ceftriaxone against 54 recent cerebrospinal fluid isolates of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae were less than or equal to 0.06 to 0.25 micrograms/ml. We examined the efficacy and safety of ceftriaxone therapy of meningitis in Bahia, Brazil. The study was conducted in two phases; in phase A, ceftriaxone was coadministered with ampicillin. The mean cerebrospinal fluid concentrations of ceftriaxone 24 h after an intravenous dose of 80 mg/kg were 4.2 and 2.3 micrograms/ml on days 4 to 6 and 10 to 12 of therapy, respectively. These concentrations were 8- to more than 100-fold greater than the 90% MBCs against the relevant pathogens. In phase B, ceftriaxone (administered once daily at a dose of 80 mg/kg after an initial dose of 100 mg/kg) was compared with conventional dosages of ampicillin and chloramphenicol in a prospective randomized trial of 36 children and adults with meningitis. The groups were comparable based on clinical, laboratory, and etiological parameters. Ceftriaxone given once daily produced results equivalent to those obtained with ampicillin plus chloramphenicol, as judged by cure rate, case fatality ratio, resolution with sequelae, type and severity of sequelae, time to sterility of cerebrospinal fluid, and potentially drug-related adverse effects. The cerebrospinal fluid bactericidal titers obtained 16 to 24 h after ceftriaxone dosing were usually 1:512 to greater than 1:2,048 even late in the treatment course, compared with values of 1:8 to 1:32 in patients receiving ampicillin plus chloramphenicol. Ceftriaxone clearly deserves further evaluation for the therapy of meningitis; the optimal dose, dosing frequency (every 12 h or every 24 h), and duration of therapy remain to be determined.

Ampicillin↗
PubMed1985

Effect of fibronectin on adherence of Staphylococcus aureus to fibrin thrombi in vitro.

Staphylococcus aureus binds to purified fibronectin in solution and may bind to fibronectin present in wound tissue. When incorporated into a solid fibrin thrombus, however, plasma fibronectin may fail to bind S. aureus, because the S. aureus-binding sites on fibronectin may be occupied by fibrin. Both S. aureus and fibrin bind to the same 27-kilodalton amino-terminal fragment of fibronectin. To determine whether fibronectin incorporated into fibrin still promotes the adherence of S. aureus, we clotted citrated normal plasma and fibronectin-depleted plasma onto petri dishes. We then measured bacterial adherence to these in vitro fibrin thrombi. We found that the adherence of five of seven S. aureus strains decreased significantly (by 26 to 58%) when fibronectin had been depleted from the fibrin thrombi. Adding fibronectin back reversed this decrease in adherence. The reversal was dose dependent; the increase was in proportion to the amount of fibronectin added back to the plasma. Bacteria known not to bind to fibronectin (Escherichia coli and Staphylococcus epidermidis) adhered 100-fold less than S. aureus, and their adherence was unaffected by the absence of fibronectin in the fibrin thrombus. We conclude that fibronectin incorporated into solid fibrin thrombi does mediate the adherence of most S. aureus strains to fibrin thrombi. Fibronectin may be an important molecule that mediates the adherence of S. aureus to fibrin in wounds.

Adhesiveness↗
PubMed1985

Hemodynamic characteristics of patients with hypothermia due to occult infection and other causes.

Eighty-five consecutive patients with hypothermia were prospectively evaluated to assess clinical and laboratory data that would differentiate those patients with hypothermia caused by severe infection and bacteremia and those with hypothermia of other causes. Thirty-two patients had hemodynamic monitoring, allowing us to assess hemodynamic differences between the two groups. Clinical characteristics, including admission temperature, leukocyte count, mean arterial pressure, pulse rate, respiratory rate, arterial pH, and pulmonary capillary wedge pressure, did not distinguish between the two groups. However, patients with infection with bacteremia had lower calculated systemic vascular resistances (486.0 +/- 125.0 compared with 1759.9 +/- 331.0 dynes.s.cm-5; p = 0.001) and higher cardiac indices (7.1 +/- 1.9 compared with 2.8 +/- 0.7 L/min X M2; p = 0.006) than patients without severe infections. Thus, our data suggest that hemodynamic characteristics are different in patients with infection-related hypothermia and patients with hypothermia associated with other causes, and appear to depend on the underlying disease.

Adult↗
PubMed1985

New cephalosporin antibiotics: selection and uses.

The new third-generation cephalosporins have an improved antibacterial spectrum and are agents of choice for the treatment of many gram-negative pathogens. With the introduction of these cephalosporins, questions on their indications and use need to be considered. It is especially important that they be saved for special situations in which their capabilities are required, which will prevent the development of widespread resistance and superinfection. A clinical summary of the new cephalosporins is provided, with emphasis on the situations in which they are agents of choice.

Anti-Bacterial Agents↗
PubMed1984

Rationale for clinical trials evaluating ceftriaxone in the therapy of bacterial meningitis.

Ceftriaxone is a promising antimicrobial agent in the therapy of bacterial meningitis. The rationale for the clinical evaluation of ceftriaxone in patients with meningitis is based on the following favorable characteristics: ceftriaxone has excellent in vitro activity (MBC90 0.25 microgram/ml or less) against the major meningeal pathogens including meningococci, pneumococci, group B streptococci, Hemophilus influenzae, and Escherichia coli, but it is inactive against Listeria monocytogenes; ceftriaxone is rapidly bactericidal within purulent cerebrospinal fluid in experimental animal models of meningitis induced by pneumococci, group B streptococci, H. influenzae, and E. coli; against most of the major meningeal pathogens, the activity attained in cerebrospinal fluid in human subjects with bacterial meningitis is high (1:512 or greater) and active concentrations of ceftriaxone persist in cerebrospinal fluid for prolonged periods compared with those of other cephalosporins; the results of clinical trials reported to date in patients with meningitis are encouraging. Ceftriaxone deserves further clinical evaluation in the treatment of bacterial meningitis; the optimal dose, frequency of administration, and duration of therapy remain to be determined.

Animals↗
PubMed1984

Principles in the treatment of bacterial meningitis.

The pathophysiologic aspects of bacterial meningitis impose some specific requirements on successful antimicrobial therapy of this disease. Because infections of the subarachnoid space rapidly produce destruction of the brain tissue, treatment must be instituted as early as possible. In the subarachnoid space, efficient host defense mechanisms are absent, particularly at the start of the infection, and therefore antibiotics have to produce a bactericidal effect to eliminate the microorganisms. As animal studies indicate, only drug concentrations 20- to 100-fold higher than the minimal bactericidal concentration are effective in vivo. Because penetration of antibiotics to the site of infection is limited by the blood-brain barrier, the high cerebrospinal fluid concentrations necessary to kill the bacteria may be difficult to achieve and therapy may be limited by toxicity. Even with optimal antibiotic therapy, the morbidity and mortality remain high, and new therapeutic interventions are necessary and should be aimed at modifying selective components of the inflammatory process.

Animals↗
PubMed1984

Pathogenesis of bacterial meningitis: contributions by experimental models in rabbits.

Rabbits models of bacterial meningitis have contributed substantially to our understanding of the disease, although the technical characteristics of these models only allow the study of specific aspects of the disease. Bacterial multiplication in the subarachnoidal space is not substantially influenced by host defense mechanisms, mainly because of the lack of sufficient amounts of specific antibodies and functional complement in infected CSF. The multiplying bacteria induce profound changes in the blood-brain barrier, an influx of serum proteins into the CSF and the invasion of polymorphonuclear leukocytes at the site of the infection. The presence of polymorphonuclear leukocytes in CSF not only appears to be of limited value in combating the infection, but also seems to produce deleterious effects on the central nervous system. Components of the leukocytes, such as unsaturated fatty acids, arachidonic metabolites and free oxygen radicals, may contribute to the profound hydrodynamic, structural and metabolic changes that are currently under study in experimental models of the disease. A better understanding of the pathophysiology of bacterial meningitis may allow us to design more effective therapeutic strategies and improve the outcome of this disease.

Animals↗
PubMed1984

Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae.

In order to define the characteristics of the antibacterial activity of beta-lactam antibiotics in the treatment of bacterial meningitis, the relationship between cerebrospinal fluid (CSF) drug concentrations and the rate of bacterial killing was investigated for penicillin G and four new cephalosporins in an animal model of meningitis due to Streptococcus pneumoniae. All five drugs showed a significant correlation between increasing drug concentrations in CSF and increasing bactericidal rates. Minimal activity was observed in CSF at drug concentrations of approximately the broth minimal bactericidal concentration (MBC). Maximal activity occurred with CSF concentrations 10-30 times higher. In vitro tests did not reproduce the unique correlation of increasing drug concentrations and killing activity found in vivo. When evaluating new beta-lactam antibiotics for the treatment of bacterial meningitis, it is reasonable to establish a minimum standard of CSF drug concentrations of greater than or equal to 30 times the MBC against the infecting organism.

Animals↗
PubMed1984

The postantibiotic effect in the treatment of experimental meningitis caused by Streptococcus pneumoniae in rabbits.

The relevance of a postantibiotic effect in the treatment of pneumococcal meningitis was evaluated in a rabbit model. After administration of a single intravenous bolus of ampicillin at various dosages, such an effect was observed in all animals. The duration of this effect in vivo (2.5-18 hr) was consistently longer than that in vitro (1-4.3 hr); however, in rabbits the postantibiotic effect was eliminated by the administration of intravenous plus intracisternal beta-lactamase. In an assessment of the potential therapeutic benefit of the postantibiotic effect, the efficacy to two regimens of treatment with different intervals between doses was compared. One group of animals received ampicillin every 4 hr and another every 12 hr. With sufficiently high doses, drug concentrations in cerebrospinal fluid exceeded the minimal bactericidal concentration for most of the 4-hr interval but for only about one-third of the 12-hr interval. The rate of cure was similar for the two regimens and approximated 100% when peak drug concentrations in cerebrospinal fluid exceeded the minimal bactericidal concentration by at least 10-fold.

Ampicillin↗
PubMed1984

Endocarditis due to methicillin-resistant Staphylococcus aureus in rabbits: expression of resistance to beta-lactam antibiotics in vivo and in vitro.

Whether a strain of methicillin-resistant Staphylococcus aureus susceptible to cephalothin by the disk-diffusion method was also susceptible to cephalothin in vivo was evaluated in the rabbit model of endocarditis. Rabbits with aortic-valve endocarditis due to methicillin-resistant S. aureus that were treated for four days with cephalothin had the same numbers of organisms in vegetations as did untreated rabbits. Treatment with cephalothin caused emergence of a highly resistant subpopulation in aortic-valve vegetations. Organisms highly resistant to cephalothin were also highly resistant to nafcillin. Thus broth-dilution and disk-diffusion tests may not predict therapeutic failure for cephalothin against strains of methicillin-resistant S. aureus. Because of cross-resistances among beta-lactam drugs, these strains should be considered uniformly resistant to this general class of antimicrobial agents, regardless of results from these tests.

Animals↗
PubMed1984

Single versus combination antibiotic therapy for pneumonia due to Pseudomonas aeruginosa in neutropenic guinea pigs.

Studies of therapy for experimental pneumonia due to Pseudomonas aeruginosa have failed to document beta-lactam-aminoglycoside synergy for most antibiotics examined, in contrast to results usually observed with pseudomonas infections at other sites. The neutropenic guinea-pig model of pseudomonas pneumonia was modified to resemble more closely therapy for clinical infections. Animals were treated 16 hr after infection with ticarcillin, azlocillin, ceftazidime, tobramycin, and netilmicin, alone and in combination. As predicted by in vitro synergy testing, in all cases combination drug therapy was more effective than the corresponding drugs given alone (P less than .05), as assessed by quantitative lung culture. Among single-drug regimens, those in which peak antibiotic levels did not exceed the minimal bactericidal concentration for the organism were significantly less effective. Resistance to aminoglycosides did not develop during therapy, and therefore, in this study does not explain the mechanism of synergy observed with beta-lactam antibiotics.

Agranulocytosis↗
PubMed1984

Teicoplanin versus nafcillin and vancomycin in the treatment of experimental endocarditis caused by methicillin-susceptible or -resistant Staphylococcus aureus.

In rabbits with experimentally induced endocarditis, the efficacy of teicoplanin compared favorably both with that of nafcillin for infection by a methicillin-susceptible strain of Staphylococcus aureus and with that of vancomycin for infection by a methicillin-resistant strain of S. aureus. In a 4-day treatment regimen, teicoplanin was as effective as either nafcillin or vancomycin in eliminating organisms from aortic valve vegetations in the respective infection. In a 10-day regimen for methicillin-resistant S. aureus endocarditis, both teicoplanin and vancomycin sterilized the vegetations of some rabbits, but the relapse rate was high for both. These results justify further investigation into the role of teicoplanin for the treatment of serious infections caused by S. aureus.

Animals↗
PubMed1984

Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis.

Experiments were performed to identify the chemoattractant for polymorphonuclear leukocytes that appears in the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis. Meningitis was induced in anesthetized New Zealand white rabbits by injecting 10(4) cells of stationary-phase Streptococcus pneumoniae type III intracisternally. Before bacteria were injected, cerebrospinal fluid contained neither polymorphonuclear leukocytes nor chemotactic activity. Significant chemotactic activity for rabbit polymorphonuclear leukocytes was detected 12 h after inoculation with bacteria and was maximal after 18 to 20 h. Chemotactic activity appeared in cerebrospinal fluid while concentrations of pneumococci and total protein were increasing but before there was any accumulation of polymorphonuclear leukocytes. The chemotactic activity in cerebrospinal fluid was heat stable (56 degrees C for 30 min), eluted from Sephadex G-75 with a profile identical to that of the chemotactic activity in zymosan-activated rabbit serum, and was inhibited by treatment with antibodies to native human C5. In addition, preincubation of polymorphonuclear leukocytes with partially purified rabbit C5a selectively inhibited their subsequent chemotactic responses to cerebrospinal fluid. These data indicate that complement (C5)-derived chemotactic activity appears in cerebrospinal fluid during the course of experimental pneumococcal meningitis in rabbits and suggest that this activity accounts for the accumulation of polymorphonuclear leukocytes observed in this infection.

Animals↗
PubMed1984

Tissue factor is a major stimulus for vegetation formation in enterococcal endocarditis in rabbits.

We examined the possible mechanisms of local initiation of coagulation in vegetation formation in enterococcal endocarditis by using a rabbit model. Contact activation and tissue factor expression by freshly excised aortic valves were assessed using assays developed for use with cultured cells. Bacteria alone lacked procoagulant activity and contact activation of plasma by excised valves did not occur. 4-d infected but not control valves expressed significant tissue factor activity (231 +/- 17 mU vs. 51 +/- 7 SE), which did not correlate with numbers of bacteria in vegetations. Tissue factor activity was also present in valves from rabbits infected for 1 and 2 d, as well as those from granulocytopenic and monocytopenic animals. Our findings suggest that tissue factor, expressed by host cells in response to infection, is a major stimulus for fibrin deposition in vegetation development.

Animals↗