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Biomedical subjects

J Carrizosa

Publications and source records attributed to J Carrizosa.

14 recordsLinked to original sources
PubMed1979

Treatment of experimental Staphylococcus aureus abscesses: comparison of cefazolin, cephalothin, cefoxitin, and cefamandole.

Cefazolin (CZ), cephalothin (CF), cefoxitin (CX), and cefamandole (CM) were evaluated in therapy of Staphylococcus aureus infection produced in perforated table tennis balls placed intraperitoneally in rabbits. Four weeks after placement of two balls in each rabbit, a beta-lactamase producing strain of S. aureus was injected into one of the balls. Twenty-four hours later therapy was initiated with 40 mg of CZ or 80 mg of CF, CX, or CM per kg intramuscularly every 6 h. After 24 h of treatment, the mean log(10) colony-forming units per ml were 7.1 for CZ, 6.7 for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean log(10) colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM. After 8 days, the titers were 1.6/ml for CZ, 1.0 for CF, 1.9 for CX, and 3.6 for CM. CZ serum levels were about double CF and CX levels and about two-thirds of CM levels. In sterile ball fluid CZ and CM levels were more than double CF or CX concentrations. Concentrations of all four antibiotics were lower in infected balls.

Abscess↗
PubMed1979

Effectiveness of nafcillin, methicillin, and cephalothin in experimental Staphylococcus aureus endocarditis.

Nafcillin, methicillin, and cephalothin (40 mg/kg every 6 h) were all effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. Nafcillin and methicillin reduced the number of S. aureus at a significantly faster rate than did cephalothin. Nafcillin and methicillin also reduced titers of the S. aureus more rapidly than did cephalothin in vitro, both in broth and in rabbit serum.

Animals↗
PubMed1978

Treatment of experimental Staphylococcus aureus endocarditis: comparison of cephalothin, cefazolin, and methicillin.

The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.

Animals↗
PubMed1978

Penicillin and netilmicin in treatment of experimental enterococcal endocarditis.

Successful therapy of enterococcal endocarditis requires the use of a combination of penicillin plus an aminoglycoside. The effectiveness of penicillin (Pen), streptomycin (Str), and netilmicin (Net), a new aminoglycoside, alone and in combination, were studied in vitro and in the treatment of left-sided enterococcal endocarditis in rabbits. In vitro Pen+Str or Net resulted in a more rapid and more complete bactericidal effect than Pen, Str, or Net alone against a Str-susceptible strain of enterococcus (strain 1). Against a highly Str-resistant strain (strain 2), Pen+Net showed an advantage over Pen, Str, or Net alone, or Pen+Str. Endocarditis was produced in rabbits with strain 1 or 2, and treatment was initiated 24 h later. Rabbits were treated for 48 h or 5 days with procaine Pen, Pen+Str, or Pen+Net. With strain 1, numbers of enterococci in the vegetations decreased more rapidly with Pen+Str or Pen+Net treatment than with Pen, Str, or Net alone. With strain 2, Pen+Net showed a clear advantage over Pen, Str, Net, or Pen+Str. Net in combination with Pen showed synergistic in vitro activity and was more effective than Pen alone in the treatment of enterococcal endocarditis in rabbits caused by both Str-susceptible and Str-resistant strains.

Animals↗
PubMed1978

Experimental streptococcal endocarditis. The early vegetation.

Aortic valve vegetation were studied in rabbits before and after intravenous injection of streptococcus mitis. Uninfected vegetation sections revealed compact eosinophilic masses with smooth-appearing edges and scattered polymorphonuclear leukocytes inside and on the surface. Scanning electron microscopic views demonstrated erythrocytes, small leukocytes, and platelets; the surface was markedly irregular. Fifteen minutes after injection of 10(10) streptococci, large mononuclear cells and polymorphonuclear leukocytes lined the vegetation edge; scanning electron microscopy showed large and small leukocytes. One and six hours after infection, there were more polymorphonuclear leukocytes inside the vegetation but few superficially. Bacteria were first seen at six hours as microcolonies inside the vegetation. Twenty-four-hour sections showed large bacterial colonies inside with few bacteria at the edges. Despite the smooth appearance of the vegetation edges, all electron microscopic views revealed very rough surfaces.

Animals↗
PubMed1977

Antibiotic concentrations in serum, serum bactericidal activity, and results of therapy of streptococcal endocarditis in rabbits.

The correlation between antibiotic concentrations in serum, serum bactericidal activity, and results of therapy was studied in rabbits with streptococcal endocarditis. Five days of procaine penicillin G reduced bacterial titers to <10 per g in 12 of 14 vegetations in rabbits receiving 75,000 U intramuscularly every 6 h and 10 of 20 in rabbits given 37,500 U. Ten days of 18,750 U every 6 h did not reduce the titers. To test for cure, rabbits were treated with 75,000 U every 6 h for 10 or 20 days and then received no therapy for 7 days. At the end of the 7-day period without therapy, vegetations were sterile in five of five and eight of eight animals, respectively. Rabbits received 37,500 U every 6 h for 5, 10, or 20 days and then no therapy for 7 days, after which vegetations were sterile in one of seven, four of nine, and seven of eight animals, respectively. The median maximal serum bactericidal dilutions at 1 h were 1/16 when 75,000 U of procaine penicillin G was administered, 1/8 to 1/16 with 37,500 U, and 1/4 to 1/8 with 18,750 U. Serum bactericidal activity could not be detected in 50% of the rabbits 6 h after administration of 37,500 U. Cure was related to a median maximal serum bactericidal dilution of at least 1/8 to 1/16 1 h after penicillin administration. A median maximal serum bactericidal dilution of 1/4 to 1/8 resulted in unsuccessful therapy.

Animals↗
PubMed1977

Experimental Bacteroides fragilis endocarditis in rabbits.

A serum-resistant strain of Bacterioides fragilis that did not produce heparinase was used to study the characteristics of B. fragilis endocarditis in the rabbit experimental model. The infective dose required to produce endocarditis in 50% of rabbits was significantly lower for rabbits with left-sided intracardiac catheters (log10 6.3 colony-forming units +/- 0.6/ml) as compared with right-sided intracardiac catheters (log10 7.7 colony-forming units +/- 0.8/ml). After 3 days of infection, bacterial titers of the tricuspid vegetations were significantly lower than titers of aortic vegetations (P less than 0.01), although at 5 days the titers were similar (P greater than 0.05). The weights of tricuspid vegetations, although similar at 3 days (P less than 0.05). There were no spontaneous deaths during 12 days of infection. In rabbits with the catheter removed before infection, bacterial titers were similar to those titers in rabbits with the catheter continuously in place. This model will permit study of various drug regimens for treatment of this disease.

Anaerobiosis↗
PubMed1977

Effect of aspirin on thrombogenesis and on production of experimental aortic valvular Streptococcus viridans endocarditis in rabbits.

Because thrombus formation at the site of endothelial injury has been thought to be a critical step in the pathogenesis of bacterial endocarditis, the effect of aspirin on experimental valvular thrombosis and bacterial endocarditis in rabbits was evaluated. Aortic valvular injury and thrombosis were induced in aspirin-treated and control rabbits with intracardiac catheters. A subsequent inoculation of Streptococcus viridans resulted in the development of infective endocarditis. Rabbits were sacrificed as early as 6 hr, and the effectiveness of aspirin was determined by the weight of the sterile vegetations and the quantitation of bacteria in the thrombotic vegetation. Aspirin, in levels in excess of 50 mg/dl did not attenuate the evolution of infective endocarditis, since the formation of sterile thrombotic vegetation and bacterial endocarditis in aspirin-treated rabbits was similar to those in controls.

Animals↗
PubMed1977

Comparison of methicillin, nafcillin, and oxacillin in therapy of Staphylococcus aureus endocarditis in rabbits.

Methicillin (M), nafcillin (N), and oxacillin (OX) (400 mg administered intramuscularly every 8 hours) were compared in the therapy of left-sided endocarditis in rabbits infected with two different strains of Staphylococcus aureus. The three antibiotics were equally effective in eliminating staphylococci from cardiac vegetations. N and OX were four to eight times as active against the staphylococci as M in broth but had equivalent activity in serum. The peak M and OX levels in serum were at least twice the peak N level, but the half-life of N in the serum (2.1 hours) was about three times that of M (0.6 hours) and twice that of OX (1.1 hours). Serum bactericidal activity tests demonstrated essentially equal activity with the three antibiotics 1 and 2 hours after injection; however, at 4 and 6 hours N had an advantage over M and OX. Therefore, despite clear differences in vitro activity, protein binding, and pharmacodynamics, M, N, and OX were equally effective in therapy of staphylcoccal endocarditis in rabbits.

Animals↗
PubMed1976

Antibiotic synergism in enterococcal endocarditis.

The recognition of enterococci highly resistant to streptomycin (S) raises questions concerning the choice of aminoglycoside in treatment of enterococcal endocarditis. Left-sided endocarditis was induced in rabbits with an S-sensitive enterococcus, strain 1 (inhibited by 125 mug per milliliter S), and an S-resistant enterococcus, strain 2 (resistant to 7,500 mug per milliliter S). Treatment was initiated 6 hours, 24 hours, or 3 days after infection with procaine penicillin (P) alone, P plus S, P plus gentamicin (G), or P plus sisomicin (Si). In rabbits infected with strain 1 for 6 hours before treatment, most vegetations were sterile after 3 days therapy with each combination but not with P alone which had mean log10 colony forming units per gram of vegetation (log CFU) of 2.5. With strain 2 the log CFU were lower (1.9 to 2.6) with each combination than with P (4.0). In rabbits infected with strain 1 for 24 hours and then given 9 days of therapy, the log CFU were decreased with each combination (2.0 to 2.3) as compared with P alone (4.9). With strain 2 the log CFU were lower with P plus G or Si (1.5 and 2.5) than with P alone or P plus S (4.5 AND 4.1). In rabbits infected with strain 1 for 3 days and then given 7 days of therapy, the log CFU were 4.1 to 5.5 with each combination and 6.7 with P. With strain 2 the log CFU was 4.0 with P plus G or Si as compared with 6.4 and 6.7 for P or P + S. These studies showed little difference between the 3 antibiotic combinations with the S-sensitive enterococcus or in early (6-hour) endocarditis caused by the S-resistant enterococcus. There was a large advantage of P plus G and P plus Si over P + S in more established (24 hour or 3 day) endocarditis caused by the S-resistant enterococcus.

Animals↗
PubMed1975

In vitro activity and pharmacokinetics in patients of cefamandole, a new cephalsoporin antibiotic.

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Cefamandole was more active than cephalothin or cefazolin against Proteus mirabilis. Both cefamandole and cefazolin were as active as cephalothin against S. aureus, were slightly more active against K. pneumoniae, and were considerably more active against E. coli. All strains of indole-positive Proteus sp. were inhibited by 6.3 mug of cefamandole per ml but only 20% were inhibited by 25 mug of cefazolin or cephalothin per ml. Eighty-eight percent of Enterobacter sp. was inhibited by 25 mug of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 mug/ml in serum and levels ranged from 440 to 16,800 mug/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of >/=31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was >/=43%. The half-life of cefamandole in serum was 49 to 126 min.

Bacteria↗
PubMed1975

Experimental aspergillus endocarditis in rabbits.

Aspergillus endocarditis in man usually occurs on prosthetic cardiac valves and gives rise to large vegetations which embolize easily producing peripheral organ infarction and infection. Blood cultures are usually sterile and the disease is difficult to cure with antimicrobial agents. Aspergillus endocarditis was studied in rabbits to determine the course, degree of fungemia, and response to treatment with amphotericin B (A), 5 flucytosine (5 FC) or A + 5 FC. Polyethylene tubing was introduced into the left ventricle through the carotid artery and 24 hours later animals were inoculated with 10(4) to 10(7) spores of a strain of Aspergillus fumigatus. Large occlusive vegetations developed on the aortic valves. Spontaneous mortality reached 67 per cent after 3 days. Despite large aggregates of mycelia seen beneath a layer of amorphous material on microscopic sections, vegetations contained only 10(3) to 10(5) colony forming units (CFU) of aspergilli per gram, suggesting the aspergilli in tissues were clumped. Disseminated infection involving kidney, lung, liver, spleen, and brain occurred. Animals without intracardiac tubing which received the same inoculum of spores did not develop endocarditis, but showed evidence of disseminated infection. Blood after 24 hours of infection grew aspergilli only when large volumes were cultured and then only a small fraction of the total volume of blood obtained for culture yielded aspergilli, suggesting that the aspergilli in blood were clumped. Sterile vegetations in the absence of an intracardiac catheter were resistant to infection with aspergilli, but once established, infection with aspergilli persisted on vegetations despite removal of the catheter. Treatment of infected animals with A (1 mg. per kilogram), 5 FC (25 or 50 mg. per kilogram) or A + 5 FC daily intraperitoneally, significantly lowered the number of CFU per gram of vegetation.

Animals↗
PubMed1975

Antagonism between chloramphenicol and penicillin in streptococcal endocarditis in rabbits.

Antagonism between chloramphenicol (CHL) and penicillin (PCH) was studied in rabbits with Streptococcus viridans endocarditis. PCN alone or preceded 1 hour by CHL was injected twice a day starting 6 hours or 3 days after infection. In animals treated 6 hours after infection, vegetations contained mean log colony-forming units (CFU):3.0 per gram in PCN animals and 3.7 in PCN + CHL animals (P greater than 0.05) after 24 hours of treatment and 2.4 in PCN animals and 4.3 in PCN + CHL animals (P greater than 0.01) after 48 hours. In animlas treated 3 days after infection, vegetations contained mean log CFU: 3.8 per gram in PCN animals and 5.2 in PCN + CHL animals (P greater than 0.01) after 72 hours of treatment and 1.7 in PCN animals and 2.5 in PCH + CHL animals (P greater than 0.05) after 5 days. The antibiotic antagonism demonstrated in these studies could be reduced by injecting CHL 1 hour after PCN instead of 1 hour before PCN.

Animals↗