Biomedical subjects
Publications and source records attributed to D M Musher.
Edwardsiella tarda is an uncommon enteric bacterium which has been found generally in animal hosts and occasionally in human feces. Three cases of extraintestinal infection caused by E. tarda which are described herein include a typhoid-like illness, peritonitis with sepsis, and cellulitis from a wound acquired while fishing. The microbiology of E. tarda and the previous reports of infection due to this organism are reviewed.
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A study was undertaken to determine whether use of a condom catheter collection system (CCCS) is associated with urinary tract infection (UTI). No UTI developed in 79 episodes of CCCS use in patients who were cooperative or because of paralysis were unable to manipulate the collecting system (mean time per patient, 21.2 days; total number of patient days, 1,677). By contrast, in 15 patients who were identified prospectively as being uncooperative and who repeatedly manipulated the CCS, UTI developed in eight (53.3%) within a mean of 9.6 days. Urethral catheterization in cooperative patients during CCCS use was followed by development of UTI. Repeated interference with the proper use of CCCS and urethral catheterization during CCCS use are associated with an increased risk of UTI.
Fever patterns were studied prospectively in 200 consecutive patients referred for infectious disease consultation and retrospectively in 204 patients with selected infectious or noninfectious diseases. Most patients had remittent or intermittent fever, which, when due to infection, usually followed diurnal variation. Hectic fever occurred less commonly but was observed in patients with all categories of infectious or noninfectious diseases. Although hectic fevers were seen more frequently in patients who had documented bacteremia, there were many nonbacteremic subjects who had this pattern and others without this pattern who had bacteremia. Sustained fever nearly always occurred in patients with Gram-negative pneumonia or CNS damage, although some patients with these diseases had other patterns as well. Our data suggest that, with the possible exception of sustained fever in Gram-negative pneumonia or CNS damage, the fever pattern is not likely to be helpful diagnostically.
Anaerobic meningitis occurred in four patients in whom anaerobic bacteria had not been suspected as a possible cause. The predisposing conditions were typical of those seen in patients previously reported to have this infection and included chronic otitis media with mastoiditis, chronic sinusitis, recent craniotomy and abdominal trauma. Two of the patients had undergone immunosuppression (immunosuppressed patients); a compromised immune system may facilitate the development of anaerobic meningitis in patients with the appropritate underlying conditions. Head and neck neoplasms, head trauma, suppurative pharyngitis and laminectomy wounds are additional situations in which anaerobic meningitis occurs. Anaerobic bacterial meningitis probably occurs more often than is recognized. The cerebrospinal fluid should be transported and cultured anaerobically when meningitis develops in a patient with a predisposing condition.
Small-colony variants of gram-negative genera of Enterobacteriaceae were selected by in vitro exposure to gentamicin. These variants were shown to have decreased susceptibility in vitro to aminoglycosides. They were lethal for mice following intraperitoneal injection, with the LD50 (50% lethal dose) being the same as, or slightly less than, that for the parent organism. Variants of strain no. 2401 of Proteus mirabilis caused urinary tract infection in mice after implantation into their bladders. Although the variants grew somewhat less rapidly than did parent organisms, both parent and variant colonies alkalinized urine at the same rate. Electron microscopic study showed no differences between colonies of parents and variants. These studies indicated that small-colony variants of Enterobacteriaceae are pathogenic for experimental animals. Further, they may cause disease in humans and should not necessarily be regarded as only laboratory curiosities.
Recent in vitro susceptibility studies have shown that amikacin inhibits more than 90% of isolates of Nocardia. This study was designed to evaluate the effect of treatment with amikacin or sulfonamides on infection caused by Nocardia asteroides with the use of murine models. In an acute lethality model in which infection was induced by intraperitoneal injection, 13 (45%) of 29 mice that had been treated with amikacin survived, in comparison to zero of 39 untreated animals in the control group and one of 39 mice that had been treated with sulfadiazine (P less than 0.001 for amikacin). When infected with a strain of N. asteroides that was resistant to amikacin, all mice that were treated with amikacin and all untreated mice died. Drug therapy was also evaluated in a chronic infection model, in which abscesses were produced by an intraperitoneal injection of N. asteroides in saline. Treatment with either amikacin (P less than 0.001) or sulfonamide (P less than 0.02) for two to three weeks significantly increased the rate of resolution of these abscesses. These murine models demonstrate that amikacin has in vivo activity against Nocardia and may be potentially useful in the treatment of human disease.
A middle-aged woman developed malabsorption and severe protein-calorie malnutrition after a near-total gastrectomy for a perforated gastric ulcer. A transbronchial lung biopsy showed pulmonary infection with Torulopsis glabrata. Improvement in the patient's nutritional status was followed by clearing of the pneumonia without the need for antifungal chemotherapy.
Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.
Mice infected intravenously with Mycobacterium bovis (BCG) are 100 to 1,000 times more sensitive to the lethal effects of bacterial lipopolysaccharides (LPS). Since BCG infection results in macrophage activation and LPS may cause pathophysiological effects through interaction with this cell type, it was of interest to determine whether macrophages from BCG-infected animals were more susceptible to the toxic effects of LPS in vitro. When LPS-susceptible, C57BL/6 mice were infected with BCG, a significant reduction in the 50% lethal dose of LPS was first observed after 7 days and persisted for several weeks. Macrophages from these animals had greatly increased susceptibility to LPS in vitro, which correlated with the development of acquired cellular resistance as determined by their ability to inhibit the growth of Listeria monocytogenes. In contrast, BCG infection of C3H/HeJ mice, a strain resistant to LPS, did not alter the 50% lethal dose of LPS for these animals or increase the sensitivity of their peritoneal macrophages to LPS in vitro. These results indicate that susceptibility of BCG-infected mice to the lethal effects of LPS parallels the susceptibility of their macrophages in vitro; release of vasoactive substances from LPS-susceptible activated macrophages in vivo may be, in part, responsible for lethality.
Rabbits infected with Treponema pallidum have strikingly depressed in vivo immunoglobulin G responses to sheep erythrocytes. To gain further insight into the nature of this suppression, the immune responses of splenic and peripheral blood lymphocytes from infected rabbits to sheep erythrocytes were studied in vitro. Spleen cells from rabbits that had been sensitized with sheep erythrocytes during active syphilis had greatly decreased immunoglobulin M and G responses after in vitro incubation with sheep erythrocytes, when compared to the results obtained with cells from sensitized uninfected animals. Suppressor cells could be demonstrated in peripheral blood lymphocytes of control rabbits 6 months after sensitization with sheep erythrocytes; these cells could be removed by nylon wool filtration. When primary sensitization with sheep erythrocytes was carried out during active syphilis, these suppressor cells were not detectable in peripheral blood lymphocytes 6 to 9 months later. These findings provide further evidence that induction of immune responses may be abnormal early in treponemal infection and may help to explain the failure of the host to produce antibodies which eradicate the organism during the first 2 to 3 months of infection.
Selective adherence to host mucosal surfaces is probably a requirement for colonization and infection by bacteria. Since pharyngeal colonization may be an important determinant in the pathogenesis of pneumonia, we studied the adherence of 10 different bacteria to pharyngeal cells obtained from nonsmokers, smokers, and chronic bronchitics. Various patterns of adherence among the different groups of subjects were found. Young healthy smokers had increased adherence of Streptococcus pneumoniae type I and, to a lesser extent, S. pneumoniae type III and Staphylococcus aureus when compared with nonsmokers. Middle-aged smokers with a long history of chronic bronchitis had significantly increased adherence only of untypable Haemophilus influenzae when compared with age-matched nonsmokers. The acquisition of pneumococcal pneumonia by smokers and the role of nontypable Haemophilus species in chronic bronchitis may be determined, in part, by bacterial adherence to pharyngeal cells.
By using mice infected with strains of Brucella abortus and Brucella melitensis we examined the histological responses to infection, the relationship of histology to persistence of organisms, and the relation of persistence of organisms to the acquisition of acquired cellular resistance (ACR). Infection with B. abortus resulted in well-formed granulomas in the livers, which persisted for more than 30 days. In contrast, infection with B. melitensis produced microabscesses in the livers which resolved before 30 days. The clearance of organisms from the tissues was also different. A total of 30 days after infection, large numbers of viable bacteria were recovered from the tissues of B. abortus-infected mice whereas bacteria were no longer recoverable from B. melitensis-infected animals. ACR to Listeria monocytogenes, another intracellular pathogen, persisted for more than 30 days in B. abortus-infected mice but waned rapidly in B. melitensis-infected animals. This disappearance of ACR due to B. melitensis paralleled the clearance of bacteria from the tissues.
Two distinctly different and stable forms of Staphylococcus aureus were isolated from the blood of each of two patients with staphylococcal sepsis. In each case, one form was hemolytic and the other nonhemolytic, although both had the same biochemical reactions, phage types, and antibiotic susceptibilities, and both were virulent for mice. Variant forms of S. aureus may be selected in vivo by host factors and may be responsible for causing and/or perpetuating infection.
In an electron microscopy study of lymph nodes from syphilitic rabbits plasmablasts and plasma cells were unequivocally identified in germinal centres. Up to 20% of the plasma cells possessed unusual cytological features. Paracortical hypoplasia was shown to be associated with actively phagocytic histiocytes. These findings may reflect morphological correlates of the aberrant immune regulation which has been observed in infection with Treponema pallidum.
Acute bilateral suppurative parotitis developed in two patients with documented cirrhosis of the liver while they were in the hospital. Gram's stain and culture of purulent material obtained from the orifice of Stensen's duct disclosed Haemophilus influenzae as the sole isolate. Both patients were treated successfully with local care and antibiotics. To our knowledge, with one possible exception, infection of the parotid gland due to this organism has not been described previously.
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