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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 109 records · Page 6Linked to original sources
PubMed1986

Ciprofloxacin in experimental Pseudomonas aeruginosa meningitis in rabbits.

The potential of ciprofloxacin for the therapy of Pseudomonas aeruginosa meningitis was evaluated in an animal model by determining the penetration of the drug into CSF, its concentration-dependent killing characteristics in vivo, and its relative efficacy compared with ceftazidime and tobramycin. Meningitis was produced in 40 rabbits by intracisternal injection of 3 X 10(7) organisms. The drugs were administered intravenously over seven hours, and simultaneously serum and CSF samples were taken at 0, 1, 3, 5, and 7 h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18.4 +/- 12.3; mean +/- standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4.1 +/- 1.3). The rate of bacterial killing for animals treated with ceftazidime (100 mg/kg/h) and high doses of tobramycin (2.5 mg/kg/h) was -0.51 +/- 0.13 (log10 cfu/ml/h). This was similar to the rate of killing (-0.48 +/- 0.2) found when ciprofloxacin was infused at 5 mg/kg/h, a dose that produced a mean serum level of 6.7 +/- 4.6 mg/l, which corresponds to concentrations achievable in humans. As dosages were increased (15 and 30 mg/kg/h), the rate of bacterial killing also increased (-0.70 +/- 0.1 and -0.89 +/- 0.4 respectively; r = 0.7407; P less than 0.01). The drugs shows promise in the treatment of pseudomonas meningitis.

Animals↗
PubMed1986

Evaluation of pefloxacin in experimental Escherichia coli meningitis.

The therapeutic efficacy of the fluoroquinolone pefloxacin mesylate was compared with those of cefotaxime and chloramphenicol in a rabbit model of Escherichia coli meningitis. The mean percent penetration (+/- the standard deviation) of pefloxacin (range, 1 to 30 mg/kg per h) into cerebrospinal fluid of infected rabbits was 51.3 +/- 14.0 compared with 11.1 +/- 1.0 for cefotaxime (100 mg/kg per h) and 22.3 +/- 1.5 for chloramphenicol (60 mg/kg per h). The rate of bacterial killing (delta log10 CFU/ml per h) did not change over a dosage range of 1 to 15 mg/kg per h (-0.37 +/- 0.15, 20% sterile). At 30 mg/kg per h, the rate achieved (-0.77 +/- 0.18, 100% sterile) was comparable to that of cefotaxime (-0.88 +/- 0.23, 100% sterile) and superior to that of chloramphenicol (-0.10 +/- 0.14, 0% sterile).

Animals↗
PubMed1986

Serum bactericidal activity of rifampin in combination with other antimicrobial agents against Staphylococcus aureus.

Because rifampin-resistant strains of Staphylococcus aureus emerge during monotherapy with this drug, a search was made for potentially useful companion drugs. Bactericidal titers of spiked serum were determined, and time kill studies were performed for 10 strains of methicillin-susceptible S. aureus. We tested rifampin in combination with nafcillin, vancomycin, clindamycin, pefloxacin, ciprofloxacin, trimethoprim, teicoplanin, or erythromycin. The bactericidal activity of nafcillin, vancomycin, and teicoplanin was significantly reduced (P less than 0.05) when rifampin was added to the drug regimen. In contrast, the addition of rifampin to clindamycin or erythromycin significantly increased bactericidal activity as measured by both bactericidal titers in serum and 6-h killing rates (P less than 0.02). Bactericidal activity in serum was also increased by the addition of rifampin to trimethoprim, but rifampin-resistant strains emerged with this combination.

Anti-Bacterial Agents↗
PubMed1986

Efficacy of ciprofloxacin for experimental endocarditis caused by methicillin-susceptible or -resistant strains of Staphylococcus aureus.

The efficacy of ciprofloxacin for experimental aortic valve endocarditis in rabbits infected by either a methicillin-susceptible or a methicillin-resistant strain of Staphylococcus aureus was compared with standard therapy of nafcillin or vancomycin, respectively. After 4 days of therapy, ciprofloxacin reduced the counts of organisms in aortic valve vegetations as effectively as the standard regimen for both susceptible and resistant strains. Mean concentrations of ciprofloxacin in serum achieved 1 h after a dose exceeded the MBC for each strain by twofold or less. In these experiments ciprofloxacin was as efficacious as standard regimens currently used to treat staphylococcal infections in humans.

Animals↗
PubMed1986

Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits.

We examined the role of fever as a host defense in experimental pneumococcal meningitis in rabbits. Twelve hours after intracisternal inoculation of an encapsulated type 3 Streptococcus pneumoniae strain, body temperature was manipulated by using two different anesthetic drugs: pentobarbital, which did not affect temperature, and urethane, which mitigated the febrile response to infection. Growth rates of pneumococci in cerebrospinal fluid were dramatically influenced by modification of the febrile response. Rabbits whose fever was not suppressed had mean bacterial doubling times of 2.76 +/- 1.43 h. Animals with a blunted febrile response had a significantly faster mean bacterial growth rate (doubling time = 1.10 +/- 0.27 h; P less than 0.02). When the antipyretic effect of urethane was counteracted by raising the ambient temperature, animals also showed a marked reduction in pneumococcal growth rates. In vitro, the pneumococci grew well at 37 degrees C in Trypticase soy broth (doubling time = 0.61 +/- 0.05 h) and in pooled rabbit cerebrospinal fluid (doubling time = 0.85 +/- 0.07 h). However, at 41 degrees C neither medium supported growth. Thus, body temperature appears to be a critical determinant of pneumococcal growth rates in experimental meningitis, and fever could be a host defense in this disease.

Animals↗
PubMed1986

Experimental models of CNS infections. Contributions to concepts of disease and treatment.

Lessons learned from studies of experimental meningitis and brain abscess in animal models of infection represent major, highly significant contributions to our understanding of the pathogenesis and antimicrobial chemotherapy of these infections. For example, studies of experimental meningitis in rabbits demonstrated that the subarachnoid space is deficient in local host defenses, a finding that explains why only bactericidal antibiotic regimens are effective in treating this disease; studies of the efficacy of corticosteroids as adjunctive therapy for meningitis yielded data indicating that both beneficial and detrimental effects on the host are imparted by these compounds. These and a number of other key investigations of experimental meningitis and brain abscess, the results of these investigations, and the clinical significance of these results are presented in this article.

Animals↗
PubMed1986

Clinical aspects of adult epiglottitis.

Epiglottitis in adults has been considered a medical rarity. Recent evidence suggests that this disorder is seen in adults regularly, though uncommonly, in clinical practice. We present 14 cases of adult epiglottitis. Most cases were blood culture-negative; Hemophilus influenzae was isolated from blood cultures in two cases and Hemophilus parainfluenzae in one case. There were no deaths. Epiglottitis in adults differs from pediatric epiglottitis in the mode of presentation, bacterial cause and clinical course.

Acute Disease↗
PubMed1985

Pathogenesis of endocarditis.

The pathophysiology of infective endocarditis comprises at least three critical elements: preparation of the cardiac valve for bacterial adherence, adhesion of circulating bacteria to the prepared valvular surface, and survival of the adherent bacteria on the surface, with propagation of the infected vegetation. It appears that circulating bacteria do not readily adhere to normal endothelial surfaces. Trauma to the valve, however, produces an alteration in the endothelial cells, leading to either disruption of the surface and deposition of platelets and fibrin, or other phenomena that render the surface susceptible to colonization by circulating bacteria. Once the surface is prepared, some bacterial strains appear to adhere to the fibrin-platelet matrix more avidly than others. The bacterial virulence factors that promote adherence are complex, but at least one, an extracellular polysaccharide (dextran), has been identified. Adherence can be blocked by antibodies directed against various surface structures. The survival of bacteria adherent to the surface of the vegetation appears to be complex as well, requiring resistance in situ to the bactericidal properties of complement and phagocytosis by white cells. In addition, vegetation propagation involves activation of the clotting cascade. For at least some streptococci, this occurs partly through perturbation of the valvular cells to produce tissue factor (tissue thromboplastin), which results in the deposition and growth of a fibrin-platelet clot over the rapidly growing bacterial colonies.

Animals↗
PubMed1985

Effects of ampicillin and corticosteroids on brain water content, cerebrospinal fluid pressure, and cerebrospinal fluid lactate levels in experimental pneumococcal meningitis.

A study was made of the effects of antibiotics and corticosteroids on parameters that reflect brain dysfunction and potential neurological damage in experimental pneumococcal meningitis in rabbits. Brain water content was 398 +/- 10 g/100 g dry weight in normal rabbits and 410 +/- 11 g in rabbits after 24 hr of infection (P less than .001). Cerebrospinal fluid (CSF) lactate levels increased from 16.3 +/- 3.4 mg/dl to 69.5 +/- 28.2 mg/dl (P less than .001), and CSF pressure increased by +8.3 +/- 3.6 mm Hg (P less than .005) over the same interval. Antibiotic therapy with ampicillin sterilized CSF and normalized CSF pressure and brain water content in all animals within 24 hr, while CSF lactate levels remained elevated. Administration of methyl prednisolone, 30 mg/kg, or dexamethasone, 1 mg/kg, 15 and 22 hr after infection completely reversed the development of brain edema, but only dexamethasone also significantly reduced the increase in CSF lactate level (43.8 +/- 12.3 mg/dl) and CSF pressure (+1.8 +/- 2.7 mm Hg). Methyl prednisolone did not significantly affect pressure or lactate levels.

Adrenal Cortex Hormones↗
PubMed1985

Penicillin therapy for treatment of experimental endocarditis caused by viridans streptococci in animals.

We studied the efficacy of penicillin and penicillin combined with streptomycin in the treatment of experimental endocarditis caused by viridans streptococci that are susceptible, tolerant, or relatively resistant to penicillin. Rabbits with experimental endocarditis were treated with procaine penicillin (1.5 X 10(5) U/kg) administered twice daily or with procaine penicillin (1.5 X 10(5) U/kg) plus streptomycin (20 mg/kg) administered twice daily for five days. Compared with control animals, animals treated with penicillin alone experienced a significant reduction (P less than .001) of colony forming units per gram of cardiac valve vegetations when infected with streptococci that are susceptible, tolerant, or resistant to penicillin. This antibiotic alone was less effective against streptococci that were tolerant or resistant to penicillin than against streptococci susceptible to the drug (P less than .01). The combination of penicillin and streptomycin was more effective therapy than was penicillin alone in animals with penicillin-tolerant or penicillin-resistant streptococci causing endocarditis (P less than .01). Penicillin-streptomycin therapy was less active against penicillin-resistant strains than against either penicillin-tolerant (P less than .04) or penicillin-susceptible (P less than .01) strains. The results of our study suggest that tolerance or relative resistance to penicillin in strains of viridans streptococci influences the response to therapy with penicillin alone or penicillin combined with streptomycin in the treatment of experimental endocarditis caused by viridans streptococci.

Animals↗
PubMed1985

Correlation of antibacterial activities of antibiotics in vitro and in animal models of infection.

Laboratory tests of antibiotic activity in vitro, ranging from simple MIC determinations to sophisticated, computerized models for studying the effects of simulated plasma concentration-time curves of antibiotics in broth, differ inherently from tests in vivo in both the general and specific variables. There are therefore likely to be discrepancies between the results obtained. Apart from the obvious lack of host-defence mechanisms in the in-vitro tests systems, the reasons for these discrepancies have still not been fully elucidated. For the time being, it seems unrealistic to expect that in-vitro tests could be developed that would make it possible to predict the efficacy of any antibiotic against any specific infection in vivo.

Animals↗
PubMed1985

Effects of sub-bactericidal concentrations of antibiotics in experimental models of endocarditis.

Subinhibitory and sub-bactericidal concentrations of antibiotics significantly influence host-bacterial interactions. This paper reviews the pathogenesis of endocarditis and examines how subinhibitory concentrations of antibiotics may influence the course of the disease. At present significant effects have been documented only for the stage of bacterial adherence to the damaged valve.

Adhesiveness↗
PubMed1985

The influence of dosing schedules and cerebrospinal fluid bactericidal activity on the therapy of bacterial meningitis.

Bacterial meningitis represents an infection in an area of impaired host defence. Optimal therapy of meningitis requires attaining bactericidal activity within cerebrospinal fluid (CSF). Studies in experimental animal models of meningitis suggest that maximal rates of bacterial killing in vivo and optimal cure rates are achieved when CSF antibiotic concentrations exceed the MBC of the test strain by greater than or equal to ten-fold. The results of clinical trials support this conclusion. In addition, a variable post-antibiotic effect occurs in-vivo after short periods of exposure to antimicrobial activity, thus maintaining therapeutic efficacy with intermittent dosage regimens. These basic principles of therapy are outlined in this review and serve as a basis for rational treatment regimens. For most antibiotics, the optimal dose, dosage interval, and duration of therapy for bacterial meningitis remain to be established.

Animals↗
PubMed1985

Therapeutic efficacy of teicoplanin in experimental enterococcal endocarditis.

The antimicrobial activities of teicoplanin and ampicillin, alone and in combination with gentamicin, were compared in experimental Streptococcus faecalis endocarditis. Bacterial titers in vegetations of rabbits treated with teicoplanin were significantly lower than those of untreated controls (P less than 0.01) and were equivalent to titers in ampicillin-treated animals. Gentamicin increased the activities of both drugs to a comparable degree.

Ampicillin↗
PubMed1985

Antimicrobial activity of gentamicin in experimental enterococcal endocarditis.

The in vitro activity of gentamicin was compared with its therapeutic efficacy in rabbits with Streptococcus faecalis endocarditis. The test strain was resistant to gentamicin as measured by MICs and MBCs determined in Mueller-Hinton broth alone or in broth supplemented with 50% rabbit serum. Gentamicin also failed to manifest anti-enterococcal activity when evaluated by time-kill studies in broth. However, the addition of serum to the medium did enhance the activity of gentamicin. In the therapy of experimental endocarditis, gentamicin used alone demonstrated anti-enterococcal activity equivalent to that of ampicillin used alone. Vegetation titers in animals treated with gentamicin alone were lower than those of untreated controls (P less than 0.01) and comparable to those in animals treated with ampicillin alone. Thus, gentamicin demonstrated anti-enterococcal activity in vivo despite the resistance observed in vitro, as measured by conventional assays to determine MICs and MBCs.

Ampicillin↗
PubMed1985

Influence of the developmental state of valvular lesions on the antimicrobial activity of cefotaxime in experimental enterococcal infections.

Cefotaxime has little antimicrobial activity in vitro against most strains of enterococci, as measured by conventional MICs and MBCs. However, the MICs of cefotaxime against many enterococci are markedly reduced by the addition of serum to the test medium. To assess the relevance of this observation in vivo, we examined the efficacy of cefotaxime in experimental Streptococcus faecalis endocarditis. Since response to antimicrobial agents may vary with the degree of vegetation development, therapeutic efficacy was assessed both in rabbits with newly formed vegetations and in rabbits with well-developed endocardial lesions. Peak serum levels of cefotaxime (50.1 +/- 20.0 micrograms/ml) exceeded the MIC in medium supplemented with serum (4 micrograms/ml), but not in Mueller-Hinton broth alone (greater than 64 micrograms/ml). After 4 days of therapy, animals with newly formed lesions (therapy initiated 1 h after infection, transvalvular catheters removed) had lower mean vegetation bacterial titers than did untreated controls. Among animals with mature vegetations (therapy initiated 12 h after infection, catheters indwelling), the rate of mortality was significantly reduced by cefotaxime therapy. However, no difference in vegetation titers was observed. Thus, cefotaxime demonstrated antienterococcal activity within newly formed vegetations, but did not inhibit bacterial proliferation within well-established vegetations.

Animals↗
PubMed1985

New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits.

Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs.

Animals↗