Richard E. Bryant

Gram-negative bacillary endocarditis: Interpretation of the serum bactericidal test

Although the serum bactericidal test is commonly used in the management of infective endocarditis, little has been written about its validity or limitations. We report three cases of gram-negative bacillary endocarditis (Pseudomonas aeruginosa, Vibrio fetus and Serratia marcescens) encountered in 1 year at a Veterans Administration hospital. Serum bactericidal titers were considered necessary to identify inadequate antibiotic regimens or to avoid unnecessary drug toxicity. The limitations of the test, particularly those pertaining to gram-negative infections, are reviewed. Misleading results during treatment with aminoglycoside antibiotics could be due to the tendency of serum to become alkaline on standing. A detailed study of the interaction of the complement-dependent bactericidal system of serum with eight antibiotics is presented. In the context of the serum bactericidal test, the interaction was additive or synergistic in 15 of 16 determinations, indicating the need to include a control study of serum sensitivity of the infecting microorganism in each case.

Chronic Osteomyelitis caused by Staphylococcus Aureus: Controlled Clinical Trial of Nafcillin Therapy and Nafcillin-Rifampin Therapy

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P=.2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

The treatment of chronic open osteomyelitis of the tibia in adults.

The treatment of 30 consecutive adult patients with chronic draining osteomyelitis of the tibia was reviewed. There were four treatment patterns. Eight patients had local débridement with or without soft tissue coverage procedures or bone graft. Three patients had radical débridement and bone transport using a circular frame. Eight patients were treated by the Papineau grafting technique after débridement. Eleven patients had débridement and circular frame fixation to correct associated nonunion, malunion, or shortening. All patients received long-term antibiotic therapy. At an average of 6 years’ followup (minimum, 2 years), two patients had persistent drainage and one patient had an aseptic nonunion. This experience affirms the value of the circular frame, of the Papineau graft, of bone transport, and of long-term antibiotics for treatment of chronic osteomyelitis of the tibia. There was successful limb salvage in all of the patients and successful treatment (fracture healing without drainage) in 27 of 30 patients. Level of Evidence: Therapeutic study, Level III-1 (case-control study). See the Guidelines for Authors for a complete description of levels of evidence.

Effect of the Abscess Environment on the Antimicrobial Activity of Ciprofloxacin

The present studies were conducted to identify factors in human purulent material that might limit or enhance the activity of ciprofloxacin against bacteria causing suppurative infection. Ciprofloxacin, imipenem, and ampicillin were tested with regard to binding or inactivation by pus. The bactericidal activity of ciprofloxacin and imipenem were tested against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, or Staphylococcus aureus in human pus with a pH of 6.0 incubated at 37 degrees C under aerobic or anaerobic conditions. The effect of single or combination drug therapy with 20 mg/kg of ciprofloxacin, imipenem, or rifampin given every 12 hours was tested against E. coli or P. aeruginosa in polymicrobic murine abscesses that had been produced by subcutaneous injection of either of those organisms mixed with Bacteroides fragilis and autoclaved human stool. Antibiotic levels and the number of bacteria surviving in pus were quantitated. Therapy of subcutaneous abscesses was delayed 72 hours to test drug efficacy against organisms in well-established infections. Levels of ampicillin, imipenem, or ciprofloxacin were reduced from 10 micrograms/ml to 3.1 +/- 4.0, 2.7 +/- 3, or 5.8 +/- 2 micrograms/ml, respectively, after incubation in eight pus specimens for 24 hours at 37 degrees C. Ampicillin levels were reduced to less than 1 microgram/ml in four pus specimens containing beta-lactamase. Imipenem levels were undetectable in two specimens and were 0.2 micrograms/ml in one specimen. Ciprofloxacin binding to pus supernate or sediment appeared to be explained by its binding to the deoxyribonucleic acid (DNA) present in pus. Activity of 5 micrograms/ml of ciprofloxacin against four E. coli or K. pneumoniae strains in pus in vitro was greater than that of twofold higher concentrations of imipenem. The bactericidal activity of ciprofloxacin and imipenem were comparable but substantially reduced against S. aureus and P. aeruginosa in pus. Ciprofloxacin alone or regimens combining ciprofloxacin with rifampin or rifampin plus imipenem reduced the number of E. coli in polymicrobic subcutaneous abscesses but had little effect on P. aeruginosa in polymicrobic abscesses. The anaerobic abscess milieu appeared to inhibit the growth of P. aeruginosa. Ciprofloxacin activity in abscess fluid did not appear to be adversely affected by acid pH, aerobic or anaerobic conditions of incubation, the abscess constituents, or the binding of ciprofloxacin to the DNA in pus. Ciprofloxacin was bound to DNA of bacterial or human origin. Binding by pus was reversible, and binding to DNA extracts of pus was blocked by pretreatment of extracts with deoxyribonuclease but not by pretreatment with ribonuclease.(ABSTRACT TRUNCATED AT 400 WORDS)

Hyphal forms in the central nervous system of patients with coccidioidomycosis.

Coccidioides immitis is a dimorphic fungus that grows as a filamentous mold in soil and as a spherule at human body temperature. The hyphal or soil form is found rarely in human tissue. We report 5 cases of coccidioidomycosis in which hyphae were found in brain tissue or spinal fluid. The presence of central nervous system plastic devices appears to be associated with morphological reversion to the saprophytic form. This reversion has implications for diagnosis and therapy and may increase the risk of obstruction of the device(s).

Hospital-acquired Klebsiella bacteremia.

Abstract: The clinical features of 27 patients with hospital‐acquired Klebsiella bacteremia were reviewed. Bacteremia usually developed late in the hospital course following surgical or manipulative procedures. Twenty‐three patients had received antibiotics prior to development of infection. Bacteremic patients who had not received prior antibiotics had undergone manipulative procedures immediately prior to infection. Klebsiella causing bacteremia were usually resistant to multiple antibiotics. However, the only feature clearly correlated with prognosis was the severity of the underlying disease.

Zinc, Iron, Copper, Selenium, Lactoferrin, and Ferritin in Human Pus

Background: Restriction of zinc and iron available for microbial growth in tissues are well‐recognized host defense mechanisms. The present studies were performed to characterize some constituents of human pus that may affect these important host defenses. Methods: Zinc, iron, copper, calcium, and magnesium in pus were measured using an atomic absorption spectrophotometer; selenium was measured fluorometrically. Ferritin was measured with a fluorometric enzyme immunoassay, and lactoferrin was measured with a radial diffusion assay. The growth of Escherichia coli at 37°C was measured in pus supernate adjusted to pH 5.5 or 7.4, in boiled supernate, or in supernate adjusted with 1.3 mM iron or 0.9 mM zinc singly or together. Results: Zinc and iron concentrations in pus exceeded normal serum. Calcium and magnesium levels were 2‐ to 3‐fold lower and higher, respectively, than normal serum values. Lactoferrin concentrations of were 880 ± 48 &mgr;g/mL and ferritin levels were 20,726 ± 2,667 ng/mL. Growth of an E coli strain was inhibited in pus at pH 5.5 but not at pH 7.4, and growth was enhanced by addition of iron or zinc to E coli suspended in pus at pH 6.7. Conclusions: To our knowledge, this is the first report of the zinc, iron, copper, selenium, lactoferrin, and ferritin levels of human pus. These studies provide additional insight into host defense mechanisms mediated by the restriction of the bioavailability of zinc and iron in suppurative infection.

Octreotide does not alter endotoxin lethality in mice or endotoxin-induced suppression of human leukocyte migration

Octreotide, a somatostatin analog, was evaluated for its effects on long-term survival in a mouse model of endotoxemia and for its effects on endotoxin-induced suppression of human leukocyte migration. Swiss Webster mice were simultaneously rendered endotoxemic with a single intraperitoneal injection of 800 micrograms E. coli Lipopolysaccharide (LPS) and treated with one of four doses of subcutaneous (s.c.) octreotide (1.0 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.04 ml saline, or 0.001 mg/kg in 0.04 ml saline) or saline alone (fluid-resuscitated control group: 0.4 ml saline s.c.; or non-fluid-resuscitated control group: 0.04 ml saline s.c.). Octreotide was continued with or without supplemental s.c. fluid resuscitation (0.4 ml saline) at eight hour intervals for either twenty-four or forty hours. There was no statistical significance to differences in long-term survival between comparable groups of octreotide treated vs saline treated animals during the entire fourteen day period of observation. Fluid resuscitation during the first forty hours following endotoxemia induction delayed death, but did not significantly improve long-term survival. In vitro work was conducted to determine the effect of octreotide on endotoxin-induced suppression of human leukocyte migration. Octreotide at concentrations ranging from 3.05 x 10(-5) Molar to 3.05 x 10(-11) Molar had no significant effect on leukocyte migration. In this study octreotide treatment failed to improve long-term survival in mice with endotoxemia and did not alter endotoxin-induced suppression of leukocyte migration.

LOWER RESPIRATORY TRACT INFECTIONS IN ELDERLY PATIENTS WITH ASTHMA

Infection plays a significant role in the morbidity and mortality of the elderly. One population in which infection has not been adequately studied is the elderly asthmatic. This article examines the problems of lower respiratory tract infections in elderly asthmatics in the context of their host defenses, the severity of infection, and their risk of infection with specific organisms. The role of infection in the pathogenesis of asthma and consideration of prophylaxis and therapy are presented.

Comparison of pharmacological and antimicrobial properties of cefadroxil and cephalexin@@@Vergleich der pharmakologischen und antimikrobiellen Eigenschaften von Cefadroxil und Cephalexin

SummaryPharmacological and antimicrobial properties of cefadroxil, a new cephalosporin antibiotic, were compared with cephalexin. Absorption and excretion were studied in 20 healthy men. Peak concentrations of the drugs in serum were similar after ingestion of single 500 mg tablets. The concentration of cefadroxil in serum was more sustained than that of cephalexin. Levels of cefadroxil in serum after a dose of 1000 mg were approximately twice those after a 500 mg dose through 6 h. Each drug administered in a dose of 500 mg every 6 h for 24 h resulted in concentrations in serum that were similar to a single dose without accumulation. Ninety-three percent of the cefadroxil and 85% of the cephalexin were excreted in urine after ingestions of single 500 mg tablets. The urine concentration of cefadroxil was more sustained than cephalexin. Minimal inhibitory and minimal bactericidal concentrations for clinical isolates were comparable with each drug. Cefadroxil compares favorably with cephalexin in this study. Sustained levels of cefadroxil in serum and urine suggest that this drug may be given at less frequent intervals than cephalexin.ZusammenfassungDie pharmakologischen und antimikrobiellen Eigenschaften von Cefadroxil, einem neuen Cephalosporin-Antibiotikum, wurden mit denen von Cephalexin verglichen. Resorption und Ausscheidung wurden bei 20 gesunden Männern untersucht. Die Spitzenkonzentrationen der Medikamente im Serum nach Einnahme einer einzelnen 500-mg-Tablette waren ähnlich. Die Konzentration von Cefadroxil im Serum hielt länger an als die von Cephalexin. Die Serumspiegel von Cefadroxil über sechs Stunden nach einer Dosis von 1000 mg waren annähernd zweimal so hoch wie nach einer 500-mg-Dosis. Bei jeder der Substanzen führte die Gabe einer Dosis von 500 mg alle sechs Stunden über einen Zeitraum von 24 Stunden zu Serumkonzentrationen, die denjenigen einer Einzeldosis ohne Kumulation ähnlich waren. Nach Einnahme einer einzigen 500-mg-Tablette wurden 93% von Cefadroxil und 85% von Cephalexin im Urin ausgeschieden. Die Urinkonzentration von Cefadroxil hielt über einen längeren Zeitraum an als die von Cephalexin. Die minimalen Hemmkonzentrationen und minimalen bakteriziden Konzentrationen für klinische Isolate waren bei den beiden Medikamenten vergleichbar. Cefadroxil schneidet beim Vergleich mit Cephalexin in dieser Studie gut ab. Langanhaltende Spiegel von Cefadroxil im Serum und Urin lassen annehmen, daß die Substanz weniger häufig verabreicht werden kann als Cephalexin.