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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 181 records · Page 10Linked to original sources
PubMed1979

Opportunistic pneumonia: a clinicopathological study of five cases caused by an unidentified acid-fast bacterium.

Five patients had opportunistic pulmonary infection caused by acid-fast bacilli, unusual clinical presentations and a unique pathological picture. Clinically, these cases mimicked septic pulmonary emboli or bacterial pneumonia. The infection was temporally related to high-dose corticosteroid therapy, given for renal-transplant rejection in four patients and for therapy of lymphocytic lymphoma in one. Histologic sections of lung-biopsy or autopsy material showed an acute suppurative pneumonia with dense alveolar infiltration by neutrophils, without granuloma formation or caseous necrosis. Predominantly intracellular acid-fast bacilli were present. The organism failed to grow in culture on routine bacterial, fungal and mycobacterial mediums. This unusual and possibly new acid-fast organism is a probable cause of suppurative pneumonia in impaired hosts receiving corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1979

A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis.

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Adolescent↗
PubMed1979

Pulmonary infection with capsule-deficient cryptococcus neoformans.

A case of bilateral lobar pneumonia due to Crytococcus neoformans is presented. The capsule-deficient fungal organisms within tissue were suggestive of Histoplasma capsulatum. Cultures grew Cryptococcus neoformans and there was cryptococcal antigen in the serum. Pulmonary cryptococcosis and the occurrence of unencapsulated cryptococci are reviewed. The important role both culture and the latex agglutination test for cryptococcal antigen play in the differential diagnosis of systemic fungal infections with over-lapping histopathology are discussed.

Adult↗
PubMed1979

Etiology and antimicrobial therapy of acute maxillary sinusitis.

Eighty-one adults with symptoms of acute sinusitis were studied by direct needle puncture and aspiration of the maxillary sinus (105 sinuses). Fifty-nine bacterial strains were isolated in titers of greater than or equal to 10(4) colony-forming units/ml; Streptococcus pneumoniae and Haemophilus influenzae accounted for 64% of the isolates. Other bacteria recovered included anaerobes (12%), Neisseria species (8.5%). Streptococcus pyogenes (3%), alpha-hemolytic Streptococcus (3%), non-group A beta-hemolytic Streptococcus (3%), Staphylococcus aureus (2%), Pseudomonas aeruginosa (2%), and Escherichia coli (2%). Viruses were isolated from 11 sinuses; these isolates included rhinovirus (six), influenza A (H3N2) virus (three), and two types of parainfluenza virus (one each). The efficacy of therapy with orally administered ampicillin, amoxicillin, or trimethoprim-sulfamethoxazole was evaluated by a repeat sinus puncture and culture. Clinical and bacteriologic responses to all three regimens were good.

Adult↗
PubMed1979

Species-specific resistance to antimocrobial synergism in Streptococcus faecium and Streptococcus faecalis.

Combinations of penicillin with various aminoglycosidic aminocyclitols were tested against a collection of clinical isolates of Streptococcus faecium in vitro and were used to treat endocarditis caused by S. faecium in the rabbit model. S. faecium proved more resistant to penicillin than Streptococcus faecalis. Even more striking, however, was the resistance to in vitro synergism by combinations of penicillin and various aminoglycosides. At clinically achievable concentrations, penicillin-gentamicin was the only combination that was synergistic against all strains that were tested. Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin, respectively. Combinations of penicillin with kanamycin, tobramycin, sisomicin, or netilmicin failed to produce synergism against any of these strains. The possible clinical significance of these findings was verified by use of the rabbit model of endocarditis. Combinations of penicillin with gentamicin or streptomycin were synergistic in the therapy of endocarditis that was produced by a strain of S. faecium that did not have a high level of resistance to aminoglycosides. However, the combination of penicillin and netilmicin was no more effective than penicillin alone.

Aminoglycosides↗
PubMed1979

Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes.

A uniformly fatal, reproducible model of experimental meningitis due to Listeria monocytogenes was developed in rabbits for study of the natural progression of the disease and was used to evaluate treatment regimens. Bacterial titers in cerebrospinal fluid and pleocytosis approximated those found in humans. Therapeutic studies in vivo revealed that rifampin was less rapidly bactericidal than ampicillin or penicillin, the agents usually recommended for treatment of meningitis; that penicillin plus rifampin was no more efficacious than penicillin alone; that ampicillin demonstrated greater bactericidal activity in vivo than did penicillin; and that addition of an aminoglycoside (gentamicin) to either penicillin or ampicillin significantly enhanced their bactericidal activity in vivo. Ampicillin plus gentamicin was the most effective combination in vivo and may represent the preferred mode of therapy for listeria meningitis.

Ampicillin↗
PubMed1979

Simultaneous disseminated aspergillosis and zygomycosis in a leukemic patient.

Although the incidence of fungal infections is increasing, infections caused by more than one fungus are rare. We have described the clinical, pathologic, and mycologic findings in a leukemic patient with simultaneous pulmonary infection and systemic dissemination caused by Aspergillus fumigatus and Rhizopus sp.

Adult↗
PubMed1979

Mecillinam-ampicillin synergism in experimental Enterobacteriaceae meningitis.

The in vitro activities of mecillinam, a new beta-amidinopenicillin, and ampicillin, alone and in combination, against an Escherichia coli strain and a Klebsiella pneumoniae strain were compared, and these results were correlated with their respective activities in vivo in experimental meningitis. The mecillinam-ampicillin combination was synergistic in vitro against both strains when tested by a modified checkerboard technique (bacteriostatic synergy). However when quantitative bactericidal synergy studies were made, the relative bactericidal rate of the combination was more rapid than that of either drug alone ("bactericidal synergy") against the Escherichia coli isolate only. In a rabbit model of Enterobacteriaceae meningitis, in vivo bactericidal activity correlated with results obtained in vitro. Both drugs were administered by continuous intravenous infusion for 8 h. Serum and cerebrospinal fluid antibiotic levels were similar to those achieved in humans. Cerebrospinal fluid bacterial concentrations (colony-forming units [CFU] per milliliter) were quantitatively titrated at 2-h intervals. Both drugs, alone or the combination, were ineffective against the K. pneumoniae strain in vivo (change in titer <1 log in 8 h). In contrast, the combination produced a markedly enhanced bactericidal effect against the E. coli strain (mean +/- standard deviation, decrease of log(10) CFU per milliliter of 3.65 +/- 1.02) compared with those of ampicillin alone (decrease of log(10) CFU per milliter of 0.07 +/- 0.8) and mecillinam alone (decrease of log(10) CFU per milliliter of 1.6 +/- 0.05) (P < 0.001). When bactericidal synergism can be demonstrated for mecillinam-ampicillin in vitro in a case of gram-negative-bacillary meningitis this combination may be useful in the therapy of the illness.

Amdinocillin↗
PubMed1979

Clearance of bacteria from cerebrospinal fluid to blood in experimental meningitis.

The occurrence and importance of secondary bacteremia in the pathogenesis of and response to therapy in meningitis is uncertain. Streptococcus pneumoniae type III was injected into the cerebrospinal fluid of the cisterna magna in anesthetized, curarized dogs, and sequential simultaneous samples were obtained from the superior sagittal sinus, cisterna magna, and peripheral blood. The results show that: (i) bacteria are rapidly transported from the cerebrospinal fluid to blood but only after active multiplication within the cerebrospinal fluid, and (ii) entrance into the blood from the cerebrospinal fluid occurs before the height of the febrile response or cerebrospinal fluid pleocytosis.

Animals↗
PubMed1979

Influence of preformed antibody on experimental Streptococcus sanguis endocarditis.

The influence of preformed, anti-whole organism antibody on the development of Streptococcus sanguis endocarditis was examined in both in vivo and in vitro systems. Antibody prevented, rather than potentiated, endocarditis in rabbits. The infectious dose in 30 control animals was 10(6.5) +/- 0.33 (mean +/- standard deviation); this increased to 10(7.71 +/- 0.05 in 36 immunized animals (P less than 0.01). No differences in bacterial clearance mechanisms were apparent between groups. Antibody also prevented the adherence of S. sanguis to the constituents of nonbacterial thrombotic endocarditis (fibrin and platelets) in vitro. When preincubated in high-titer antisera, adherence of S. sanguis was reduced compared with controls (adherence ratio mean +/- standard error of the mean, X 10(4): 174 +/- 5 versus 427 +/- 10, P less than 0.001). Preadsorption of immune sera with intact S. sanguis restored adherence to normal values, whereas preadsorption with dextran was partially effective. These studies demonstrate that preformed antibody had a protective role in vivo and suggest that a possible mechanism is blockade of adherence, a crucial early step in the pathogenesis of endocarditis.

Animals↗
PubMed1979

Enzyme-linked immunosorbent assay for detection of Streptococcus pneumoniae antigen.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of Streptococcus pneumoniae polysaccharide antigen in cerebrospinal fluid and serum. Sensitivity and specificity were determined for purified antigen preparations. Specificity was also evaluated in the rabbit meningitis model, and the sensitivity was compared to counterimmunoelectrophoresis, using the infected rabbits' cerebrospinal fluid and serum. The ELISA was a specific technique for detecting S. pneumoniae antigen. ELISA was 25 times more sensitive than counterimmunoelectrophoresis for purified antigen and resulted in an increased positivity of the cerebrospinal fluid and serum from infected rabbits. ELISA should prove very useful in the diagnosis of pneumococcal infections.

Animals↗
PubMed1979

Antibiotic penetration into normal and inflamed tissues as reflected by peripheral lymph.

The concentration of antibiotic in peripheral lymph reflects the tissue levels. Following microsurgical cannulation of the right lymphatic duct in 28 healthy rabbits, either penicillin-G, nafcillin, erythromycin, or cefazolin was given intramuscularly, and lymph and serum samples obtained at frequent intervals. Penicillin or nafcillin was administered to 14 additional rabbits with cellulitis of the right upper extremity. A serum sample drawn between one and two hours after an intramuscular injection, in general, reflects the peak lymph antibiotic concentration and hence the peak tissue concentration of the drug. After two hours the lymph level remains equal to or greater than the simultaneous serum level. The presence of inflammation did not alter the peak antibiotic levels. However, nafcillin required longer for equilibration in the inflamed state than in the uninflamed state, whereas penicillin-G equilibrated more rapidly in the presence of inflammation.

Animals↗
PubMed1978

Factors influencing the therapy of experimental Proteus mirabilis meningitis in rabbits.

The therapy of Proteus mirabilis meningitis with gentamicin alone and in combination with chloramphenicol was studied in a rabbit model. Antibiotics were administered for 8 hr. Samples of serum and cerebrospinal fluid (CSF) obtained simultaneously were assayed at 2-hr intervals for antibiotic concentration and counts of bacteria in CSF. The percentage of penetration ([concentration in CSF divided by concentration in serum] x 100%) of gentamicin ranged from 14% to 23%, but very large dosages were required to kill bacteria in the CSF. Although the minimal bactericidal concentration (MBC) of gentamicin was 1 microgram/ml, killing in vivo occurred only when concentrations in CSF were 10--30 times the MBC. The high concentration required for bactericidal activity in vivo may be explained by the reduced pH of infected CSF (mean pH, 6.98; range, 6.69--7.18). The bactericidal action of gentamicin was abolished by the simultaneous administration of chloramphenicol. Titers of bacteria in CSF were reduced 2.60 log10 (mean) with gentamicin therapy vs. 0.92 log10 (mean) with combination (P less than 0.01).

Animals↗
PubMed1978

Cephalosporin antibiotics in therapy of experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis in rabbits.

Six cephalosporin antibiotics (cefamandole, cefazolin, cephacetrile, cephalothin, cephaloridine, and cephradine) and two penicillin (ampicillin and penicillin G) were evaluated in vitro and in a rabbit model of experimental meningitis due to Haemophilus influenzae or Streptococcus pneumoniae. The percentage penetration ([concentration in cerebrospinal fluid/concentration in serum] X 100%) of these antibiotics varied from 0.7% for cephalothin to 17% for cephaloridine. The penetration varied inversely with binding to serum proteins. The bactericidal rate of all of the cephalosporin antibiotics was similar in vitro and in vivo to that of penicillin G. However, as demonstrated with cephalothin, concentrations considerably above the minimal bactericidal concentration (as determined in broth) were necessary to initiate the bactericidal effect. Cefamandole was found to be as effective as ampicillin in the therapy of H. influenzae meningitis in rabbits.

Ampicillin↗
PubMed1978

Penicillin-netilmicin synergism against Streptococcus faecalis.

The combination of penicillin plus netilmicin was synergistic in vitro against 28 strains of Streptococcus faecalis and compared favorably with penicillin in combination with gentamicin. Similarly, penicillin plus netilmicin was as effective as penicillin plus gentamicin in the therapy of 67 rabbits with enterococcal endocarditis produced with a streptomycin-susceptible (S) or a streptomycin-resistant (R) strain of S. faecalis. After 5 days of infection, control rabbits had bacterial titers of 10(10) colony-forming units (CFU)/g of vegetation. Those treated with penicillin plus netilmicin had mean titers of 10(5.2) and 10(5.1) CFU/g for S and R strains, respectively, and those treated with penicillin plus gentamicin had mean valve titers of 10(5.8) CFU/g for both strains. After 10 days of therapy, mean valve titers with penicillin plus netilmicin were 10(3.8) and 10(4.7) CFU/g, and with penicillin plus gentamicin they were 10(4.5) and 10(5.4) CFU/g for S and R strains, respectively. Thus, if netilmicin proves to be less toxic than other aminoglycoside antibiotics, it may have potential usefulness in the therapy of enterococcal endocarditis.

Animals↗
PubMed1978

Comparison of netilmicin with gentamicin in the therapy of experimental Escherichia coli meningitis.

Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental Escherichia coli meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 10(5)E. coli colony-forming units. The minimum bactericidal concentration was 2 mug/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) x 100%] was 22.5 +/- 6.0 and 20.6 +/- 7.2 for netilmicin and gentamicin, respectively (P = 0.18). However, netilmicin achieved bactericidal activity in the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 mug/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 mug of netilmicin per ml as compared to 14.1 mug of gentamicin per ml. Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.

Animals↗
PubMed1978

Pharmacokinetics of cefaclor and cephalexin: dosage nomograms for impaired renal function.

The pharmacokinetics of cefaclor and cephalexin were characterized in patients with creatinine clearances ranging from 0 to 147 ml/min. Each of 24 fasted subjects received a single 500-mg oral dose of cefaclor, and 13 of these subjects later received 500 mg of cephalexin. Serum and urine levels of the antibiotics were measured by bioassay. The serum half-lives were highly correlated with corrected creatinine clearance (cefaclor r = 0.92, cephalexin r = 0.94). Linear regression estimates of the half-life of cefaclor were 2.3 h in the anephric patient and 40 min in the patient with a corrected creatinine clearance of 100 ml/min. For cephalexin, corresponding half-lives were 15.4 h and 58 min. We present a dosage nomogram for calculating the appropriate adjustments to the loading dose based on patient weight and maintenence dose based on corrected creatinine clearance.

Adult↗