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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 145 records · Page 8Linked to original sources
PubMed1984

Treatment of streptomycin-susceptible and streptomycin-resistant enterococcal endocarditis.

Fifty-six patients with enterococcal endocarditis received 4 weeks of antimicrobial therapy with penicillin G and streptomycin (36 patients) or, if infections were streptomycin resistant, penicillin and gentamicin (20 patients). Compared with patients who had symptoms for less than 3 months, patients with symptoms for more than 3 months had a higher relapse rate (0% versus 44%; p less than 0.001) and mortality (2.5% versus 25%; p less than 0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25%) than patients with aortic valve infections (0%) (p less than 0.01). Gentamicin-associated nephrotoxicity was more frequent (p less than 0.001) among patients treated with greater than 3 mg/kg d of gentamicin than among those treated with 3 mg or less (100% versus 20%). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for more than 3 months or patients with mitral valve infection should receive at least 6 weeks of antimicrobial therapy, but patients without these high-risk factors can be treated for 4 weeks.

Adult↗
PubMed1983

Amdinocillin therapy of experimental animal infections.

Amdinocillin has been shown to have broad coverage in vitro against many strains of Enterobacteriaceae. Synergy has been demonstrated in vitro with several other beta-lactam antibiotics. The rabbit model of meningitis was used to study the in vivo effectiveness of amdinocillin when combined with other beta-lactams for serious infections. Organisms that showed an enhanced in vitro bactericidal effect from the combination of amdinocillin and another beta-lactam showed more rapid elimination of the organisms in vivo.

Amdinocillin↗
PubMed1983

Double-blind randomized study of prophylactic trimethoprim/sulfamethoxazole in granulocytopenic patients with hematologic malignancies.

In a double blind study, oral prophylactic trimethoprim/sulfamethoxazole was evaluated for its utility in preventing serious infections in patients with hematologic malignancy. Of 58 evaluated granulocytopenic episodes in 47 patients, acute leukemia was the underlying malignancy in 46 episodes. Trimethoprim/sulfamethoxazole prophylaxis resulted in fewer microbiologically documented infections (seven versus 15; p = 0.029). This was primarily the result of a reduction in episodes of bacteremia in the trimethoprim/sulfamethoxazole-treated group as compared with the placebo-treated group (three versus nine episodes; p = 0.05). The combined frequency of disseminated candidiasis, candidemia, and esophagitis of presumed fungal etiology was greater in the trimethoprim/sulfamethoxazole-treated group (six) than in the placebo-treated group (two) but not significantly so (p = 0.13). Similarly, there were no significant differences between groups in the overall incidence of infectious complications, number of febrile days, use of parenteral antibiotics, or number of days following randomization to first infectious episode. Throat and rectal surveillance cultures more frequently revealed trimethoprim/sulfamethoxazole-resistant gram-negative bacilli and yeasts in the trimethoprim/sulfamethoxazole-treated group. More frequent emergence of yeast isolates from previously culture-negative patients was documented (p = 0.033). Thus, in this study, trimethoprim/sulfamethoxazole prophylaxis during granulocytopenia reduced the incidence of microbiologically documented infections. However, the emergence of resistant bacteria and of fungi may limit the potential usefulness of this approach.

Adolescent↗
PubMed1983

Diagnosis and outcome of bowel infarction on an acute medical service.

Twenty patients with surgically or pathologically documented bowel infarction are compared with seven patients who were believed to have bowel infarction but had negative findings at laparotomy. The presentation of verified bowel infarction was nonspecific; abdominal pain, tenderness, and distension were the most common, occurring in 15 patients. No physical finding or laboratory test distinguished bowel infarction from mimicking conditions. Patients in both groups had an extremely poor prognosis. An approach to management is suggested.

Abdomen, Acute↗
PubMed1983

Moxalactam for the treatment of bacterial meningitis in children.

Increasing resistance to antibiotics in meningeal pathogens has stimulated a search for new antimicrobial agents for the treatment of bacterial meningitis. Moxalactam penetrates well into infected cerebrospinal fluid (CSF) and is highly active against most gram-negative bacteria. The clinical efficacy and safety of moxalactam in the treatment of childhood meningitis caused by Haemophilus influenzae (25 patients) or Neisseria meningitidis (five patients) was evaluated in a random, uncontrolled study. The penetration of the antibiotic into CSF was also evaluated in these patients and in another five children with bacterial meningitis. The clinical results were excellent, with 29 of 30 cases cured. The single adverse clinical reaction noted was the development of a wound hematoma in a postoperative patient; this problem may have been related to moxalactam therapy. The levels of moxalactam achieved in CSF greatly exceeded the minimal bactericidal concentrations for the infecting organisms. Moxalactam appears to be safe and effective as primary therapy for meningitis caused by H influenzae or N meningitidis.

Adolescent↗
PubMed1983

Correlation of in vitro time-kill curves and kinetics of bacterial killing in cerebrospinal fluid during ceftriaxone therapy of experimental Escherichia coli meningitis.

Ceftriaxone was highly active in eliminating Escherichia coli from the cerebrospinal fluid of rabbits infected with experimental meningitis. However, concentrations equal to or greater than 10 times the minimal bactericidal concentration had to be achieved to ensure optimal efficacy (rate of kill, 1.5 log10 CFU/ml per h). In contrast to other beta-lactams studied in this model, ceftriaxone concentrations in cerebrospinal fluid progressively increased, whereas serum steady state was obtained by constant infusion. The percent penetration was 2.1% after 1 h of therapy, in contrast to 8.9% after 7 h (P less than 0.001). In vitro time-kill curves done in cerebrospinal fluid or broth more closely predicted the drug concentrations required for a maximum cidal effect in vivo than that predicted by determinations of minimal inhibitory or bactericidal concentrations.

Animals↗
PubMed1983

Value of serum tests in combined drug therapy of endocarditis.

Two in vitro tests, the serum killing level and the serum bactericidal rate assays, were evaluated for correlation with therapeutic efficacy in the rabbit model of Staphylococcus aureus endocarditis. Animals were treated with nafcillin alone and in combination with tobramycin or gentamicin. Both were effective therapies, but rapidity of vegetation sterilization by the single and combined regimens was shown by the serum bactericidal rate assay but not the serum killing level assay. As a direct measure of bactericidal activity in serum during therapy, the serum bactericidal rate assay may be a clinically useful supplemental test for providing information that the serum killing level assay cannot.

Animals↗
PubMed1983

Influence of preformed antibody on the pathogenesis of experimental Candida albicans endocarditis.

The influence of preformed antibody on the induction of experimental Candida albicans endocarditis was investigated by both in vitro and in vivo techniques. Preincubation of C. albicans with immune serum (raised in rabbits by intravenous injection of Formalin-killed yeast cells) decreased adhesion to the constituents of nonbacterial thrombotic endocarditis, e.g., fibrin plus platelets, in vitro. Two different methods, with radiolabeled or viable yeast cells, were confirmatory and demonstrated decreased adhesion of immune serum-treated C. albicans cells to 0 to 7.8% of control values (P less than 0.001). These results correlated with protection from the development of C. albicans endocarditis in the immunized rabbits. The mean (+/- standard deviation) infectious dose for 50% of the animals was 10(5.29) +/- 10(0.07) in 48 control animals versus 10(7.11) +/- 10(0.22) in 37 immunized rabbits (P less than 0.001). These studies suggest that humoral antibody may protect against C. albicans endocarditis, perhaps through inhibition of adhesion, a crucial early step in the pathogenesis of endocarditis.

Adhesiveness↗
PubMed1983

Experimental pneumococcal meningitis: role of leukocytes in pathogenesis.

Two groups of rabbits with experimental meningitis induced by direct intracisternal inoculation of Streptococcus pneumoniae cells were studied. One group was rendered profoundly leukopenic by nitrogen mustard, and the other had normal leukocyte counts. The two groups had comparable bacterial growth rates (mean generation time, 60 versus 67 min) and ultimate bacterial populations in the cerebrospinal fluid (CSF) (mean log10 CFU, 9.1 versus 8.7); therefore leukocytes did not effectively slow or limit the growth of pneumococci in the CSF in vivo. Increased CSF protein, decreased CSF glucose, and increased CSF lactate levels were similar in both groups, suggesting that leukocytes are not essential for these changes to occur. Quantitative blood cultures revealed identical levels of pneumococcal bacteremia until 13 to 14 h after the initiation of infection, when the leukopenic rabbits showed a larger number of pneumococci in the blood, ultimately exceeding the number reached in nonleukopenic rabbits by 100-fold. Leukocytes therefore limit the extent of pneumococcal bacteremia after infection of the CSF despite their lack of effect on the course or the CSF manifestations of experimental meningitis.

Animals↗
PubMed1983

Bactericidal versus bacteriostatic antibiotic therapy of experimental pneumococcal meningitis in rabbits.

A rabbit model of pneumococcal meningitis was used to examine the importance of bactericidal vs. bacteriostatic antimicrobial agents in the therapy of meningitis 112 animals were infected with one of two strains of type III Streptococcus pneumoniae. Both strains were exquisitely sensitive to ampicillin, minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC)<0.125 mug/ml. The activity of chloramphenicol against the two strains varied: strain(1)-MIC 2 mug/ml, MBC 16 mug/ml; strain(2)-MIC 1 mug/ml, MBC 2 mug/ml. Animals were treated with either ampicillin or chloramphenicol in dosages that achieved a peak bactericidal effect in cerebrospinal fluid (CSF) for ampicillin against both strains. Two different dosages were used for chloramphenicol. The first dosage achieved a peak CSF concentration of 4.4+/-1.1 mug/ml that produced a bacteriostatic effect against strain(1) and bactericidal effect against strain(2). The second dosage achieved a bactericidal effect against both strains (mean peak CSF concentration 30.0 mug/ml). All animals were treated intramuscularly three times a day for 5 d. CSF was sampled daily and 3 d after discontinuation of therapy for quantitative bacterial cultures. Results demonstrate that only antimicrobial therapy that achieved a bactericidal effect in CSF was associated with cure. Over 90% of animals treated with one of the bactericidal regimens (i.e., animals in which the bacterial counts in CSF dropped >5 log(10) colony-forming units [cfu]/ ml after 48 h) had sterile CSF after 5 d of treatment. On the other hand, the regimen that achieved bacteriostatic concentrations (CSF drug concentrations between the MIC and MBC) produced a drop of 2.4 log(10) cfu/ml by 48 h; however, none of the animals that survived had sterile CSF after 5 d. These studies clearly demonstrate in a strictly controlled manner that maximally effective antimicrobial therapy of experimental pneumococcal meningitis depends on achieving a bactericidal effect in CSF.

Ampicillin↗
PubMed1983

Patterns of antibiotic use in a busy metropolitan emergency room: analysis of efficacy and cost-appropriateness.

Antibiotics account for 15 percent to 20 percent of all new and refill prescriptions issued in ambulatory community practice. Antibiotic-prescribing practices in our emergency room for common outpatient infections-pharyngitis, bronchitis, sinusitis, otitis media, cellulitis, cutaneous abscesses and pneumonia-were evaluated. Antibiotic selection was compared with recommendations representing current standards for care, and the cost of each was approximated. Antibiotic agents were judged to be overused in patients with pharyngitis, bronchitis and cutaneous abscesses. Patients who had acute sinusitis and otitis media often did not receive antibiotics or received an antibiotic not active against Hemophilus influenzae. A simple audit of antimicrobial drug usage for common outpatient infections proved to be a cost-effective way to identify excessive or inappropriate drug use. This approach could be used for evaluating the use of other drugs, and the results of these evaluations could serve to focus continuing educational programs.

Adult↗
PubMed1983

Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts.

Data collected from a prospective multicenter study of endocarditis caused by S. aureus were analyzed to contrast the clinical presentation of the disease between a group of 46 intravenous drug addicts and a group of 35 nonaddicts. Two-thirds of the patients in each group were men. The duration of illness before diagnosis was similar (mean, 9.3 days). Intravenous-drug addicts were younger and had less underlying disease (30% versus 80%) than the non-addicts. When first seen, the drug addicts had signs and symptoms of sepsis and pulmonary embolism, but only 40% had pathologic murmurs. Seventy-six percent had evidence of tricuspid valve infection only. Congestive heart failure and neurologic manifestations were uncommon in addicts. Nonaddicts had infection involving predominantly the left side of the heart (14 mitral valves, 8 aortic valves, 4 both aortic and mitral valves) and 80% had underlying medical diseases. Only half of these patients had pathologic murmurs when first examined, but another 30% developed them later. Congestive heart failure, involvement of the central nervous system, and peripheral embolic or septic complications each occurred in over half of the nonaddicts. Eighty percent of these patients had peripheral stigmas of endocarditis. One intravenous drug addict (2%) and seven nonaddicts (20%) died. Six patients required cardiac valve replacement either during or after a course of antibiotics. Outcome was not related to the titer of peak serum bactericidal tests. Endocarditis caused by S. aureus presents as two distinct clinical syndromes depending on the patient population (intravenous drug user or nonaddict) and the location of infection (right-sided or left-sided). The disease is distinguished from endocarditis due to other causes by its acute onset and its fulminant course manifested by a multitude of septic and embolic complications and its ability to cause heart failure. Medical management alone is often successful but in certain subsets of patients, notably those with infection of aortic or multiple valves, early operation may be necessary.

Endocarditis, Bacterial↗
PubMed1982

Antimicrobial therapy for two serious bacterial infections. Enterococcal endocarditis and nosocomial pneumonia.

Enterococcal endocarditis and gram-negative bacillary pneumonia are two serious infections that are particularly difficult to treat with currently available antimicrobial agents. Enterococcal endocarditis requires two drugs--a penicillin plus an aminoglycoside--to effect cure. Therapy for highly streptomycin-resistant strains seems to be particularly troublesome. The incidence of relapse and toxic reactions are high even when penicillin and gentamicin are administered for four weeks. New drugs that are less toxic are desperately needed. Nosocomial gram-negative bacillary pneumonia is associated with an extremely high mortality. However, overdiagnosis leads to the overuse of potentially toxic antimicrobial agents. Currently, therapy is usually initiated with a beta-lactam drug and an aminoglycoside, and the incidence of toxic reactions is high. New therapeutic approaches are needed.

Aminoglycosides↗
PubMed1982

Pharmacokinetics of cefaclor in renal failure: effects of multiple doses and hemodialysis.

The pharmacokinetics of cefaclor were characterized in 15 functionally anephric patients on hemodialysis. Each patient received a 500-mg oral dose of cefaclor every 8 h for 10 days. Multiple serum drug levels were measured by bioassay on day 0 (no hemodialysis), day 10 during hemodialysis, and as single determinations 1 h after administration on days 1, 3, and 5. Analysis of cefaclor kinetics in these 15 patients along with kinetics from 24 previously studied patients showed that weight was the best single predictor of volume of distribution. The corrected creatinine clearance (calculated from serum creatinine, age, and sex) proved to be the best predictor of drug half-life (r = 0.969). Thus, a single serum creatinine test provided a better estimated of cefaclor half-life than a 24-h urine collection. Cefaclor was cleared with an average serum half-life of 2.9 h without hemodialysis and 1.5 h during hemodialysis. Cefaclor serum levels measured 1 h after administration on days 0, 1, 3, and 5 showed no evidence of accumulation. Thus, cefaclor may be administered orally in multiple doses without accumulation in functionally anephric patients. In patients on dialysis, dosage interval or quantity should be increased to compensate for doubled drug clearance dialysis.

Administration, Oral↗
PubMed1982

Clindamycin therapy of experimental Staphylococcus aureus endocarditis.

The efficacy of clindamycin in the treatment of experimental endocarditis in rabbits was compared with that of nafcillin. Both drugs were administered intramuscularly three times daily for 5 days, clindamycin at doses of 6.25, 12.5, 25, or 50 mg/kg and nafcillin at a dose of 200 mg/kg. The minimum inhibitory and bactericidal concentrations (0.125 microgram/ml) of clindamycin for the test strain of Staphylococcus aureus were very similar to the corresponding concentrations (0.25 microgram/ml) of nafcillin. The effectiveness of clindamycin against the experimental endocarditis was dose dependent. The therapeutic accomplishments of the two highest clindamycin doses were equivalent to those attained with 200 mg of nafcillin per kg. The rates of sterilization of vegetations were equal when the serum bactericidal titers of these drugs were greater than or equal to 1:8. In special situations the administration of clindamycin in high doses could prove useful in the treatment of S. aureus endocarditis.

Animals↗
PubMed1982

Comparison of cefoperazone with penicillin, ampicillin, gentamicin, and chloramphenicol in the therapy of experimental meningitis.

Cefoperazone was compared with penicillin against Streptococcus pneumoniae, gentamicin against Escherichia coli, and ampicillin and chloramphenicol against Haemophilus influenzae in the therapy of experimental meningitis in rabbits. Meningitis was produced by intracisternal inoculation into cerebrospinal fluid, and all antibiotics were administered intravenously over 8 h in dosages that would achieve serum levels comparable to those found in humans. The mean percent penetration into purulent cerebrospinal fluid, expressed as (cerebrospinal fluid concentration/serum concentration) x 100%, was 2.6% for penicillin, 22.0% for gentamicin, 12.1% for ampicillin, 23.8% for chloramphenicol, and 6.4% for cefoperazone. The mean cerebrospinal fluid antibiotic concentrations exceeded the minimum bactericidal concentration for the test strain in each experimental model, except for ampicillin in experimental meningitis due to the beta-lactamase-producing H. influenzae. Cefoperazone produced a significantly faster bactericidal effect after 4 h of treatment when compared with penicillin (P = 0.037) and ampicillin (P = 0.01) in meningitis caused by S. pneumoniae and H. influenzae (ampicillin susceptible), respectively. In meningitis caused by E. coli, cefoperazone was significantly (P = 0.006) more rapidly bactericidal after 8 h of treatment when compared to gentamicin. In addition, cefoperazone was significantly more rapidly bactericidal than either ampicillin or chloramphenicol in experimental meningitis due to beta-lactamase-producing H. influenzae. Cefoperazone deserves further evaluation in the therapy of bacterial meningitis in humans.

Ampicillin↗
PubMed1982

Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to parenteral drugs and in nonaddicts: A prospective study.

Single (nafcillin for 6 weeks) and combined (nafcillin for 6 weeks plus gentamicin for 2 weeks) drug regimens were compared in two separate multicenter prospective randomized trials. Forty-eight parenteral drug addicts and 30 nonaddicts with clinically and bacteriologically documented Staphylococcus aureus endocarditis were studied. In the addicts, combined therapy effected a more rapid mean clinical response (defervescence and normalization of leukocyte count) and a reduced duration of bacteremia in patients with right-sided endocarditis. In the nonaddicts, combined therapy effected more rapid clearance of bacteremia, but was associated with a higher incidence of azotemia. The addition of gentamicin did not alter morbidity or mortality in either group.

Adolescent↗