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Biomedical subjects

T F O'Brien

Publications and source records attributed to T F O'Brien.

At least 55 records · Page 3Linked to original sources

New concepts in medical bacteriology.

Traditional tests employed in a clinical microbiology laboratory for speciation of bacteria rely upon the presence of one or more gene products (biochemical profile) from a population of bacterial cells. These traits have been stable over a relatively long period of time, and the techniques have served us well. Current technology allows for modification and potential improvement of this system. By chemically separating DNA strands and employing recombinant DNA techniques, direct identification of bacteria becomes possible. These methods can be adapted directly to the clinical setting. In addition, specific gene products yield clinical disease; monoclonal antibodies directed against these products may speciate a bacterium indirectly through a unique gene product. Specific gene products also provide markers for epidemiologic investigation. All these technologies should find frequent clinical application in the next several years. The discoveries a century ago that germs cause infection and that different germs cause different infections prompted the development of a system of taxonomy for pathogenic microbes. It then became apparent that the identity of the germ infecting a patient could tell us more about his or her diagnosis and prognosis than could all of the clinical skills accumulated up to that time.

Anti-Bacterial Agents

Molecular epidemiology of antibiotic resistance in salmonella from animals and human beings in the United States.

We collected serotyped isolates of salmonella from reference laboratories in the United States, tested their susceptibility to antibiotics, and extracted plasmids from isolates that were resistant to a different combination of antibiotics from each of three serotypes. Restriction-endonuclease digestion showed that within each of the three groups, plasmid molecules from animal and human isolates were often identical or nearly identical. One serotype-plasmid combination appeared to be endemic in cattle in 20 states and infected 26 persons in two states. The human cases, which were not recognizably related except for their common plasmids, appeared to be clustered in time but geographically dispersed, like cases in previous outbreaks spread by food products. These findings suggest that resistance plasmids may be extensively shared between animal and human bacteria, and that spread of multiresistant strains of salmonella among animals and human beings, as observed in Britain, may have been undetected in the United States for lack of comparable surveillance.

Animals

Moxalactam therapy of infections caused by cephalothin-resistant bacteria: influence of serum inhibitory activity on clinical response and acquisition of antibiotic resistance during therapy.

Thirty patients infected predominantly by Serratia marcescens and Pseudomonas aeruginosa were treated in an open trial with moxalactam, a broad-spectrum beta-lactam antibiotic. Twenty-three (76%) had a satisfactory microbiological or clinical response. Among 25 patients for whom serum inhibitory concentrations were measured, those with favorable microbiological responses had significantly higher values than those with poor responses (reciprocal geometric mean concentrations, 49 versus 4.9; P less than 0.01). A serum inhibitory concentration of greater than 1:8 correlated significantly with a favorable outcome (17 of 18 versus 2 of 7 responses; P less than 0.01). Although the overall clinical efficacy of moxalactam was good, resistant organisms of species identical to those of the original infecting isolates were recovered during therapy in seven cases, including five caused by Pseudomonas organisms and two caused by Serratia organisms.

Adult

Dissemination of an antibiotic resistance plasmid in hospital patient flora.

The 2'' aminoglycoside nucleotidyltransferase, AAD (2''), which adenylates gentamicin, tobramycin, and kanamycin, became prevalent over several months in multiple strains and species of Enterobacteriaceae isolated at one hospital. Eight plasmids with the gene for this enzyme purified from different strains and species isolated at different times had similar EcoRI digestion fragments, indicating that the gene had disseminated on one plasmid without transposition. This 56.5-megadalton plasmid of incompatibility group M, which also carried three other resistance genes, spread, at first, largely in one strain of Klebsiella pneumoniae, which later disappeared. It transferred to some strains which tended not to colonize other patients and later circulated predominantly in Serratia marcescens. Computer surveillance of routine hospital laboratory results was able to detect and trace the gene and the plasmid and measure their effect on resistance prevalence.

Aminoglycosides

International comparison of prevalence of resistance to antibiotics.

Prevalence of bacterial resistance to antibiotics was found to be substantially different in two separate regions of the world. The average percent resistant to individual antibiotics was nearly three times greater, and the percent of isolates resistant to six or more antibiotics 14 times greater among isolates at the Hôpital St Joseph in Paris than among those at the Peter Bent Brigham Hospital in Boston or at any of six US hospitals. Differences were not due to culture sampling or susceptibility testing methods used in the hospitals. Differences were nearly as great between isolates from patients recently admitted to the two hospitals, suggesting differences in the bacterial flora of their communities. Similar systematic comparisons of resistance prevalence in different parts of the world might help to define optimal antibiotic usage practices.

Anti-Bacterial Agents

Differential diagnosis of intrahepatic shadowing on ultrasound examination.

Significant sonic shadowing originating from a structure within the hepatic parenchyma is unusual and often denotes pathology. The differential diagnosis (choledocholithiasis, air in the biliary tree, calcified tissue, foreign bodies, and shadowing from normal structures) is reviewed and examples are presented.

Adult

Unusual echographic appearance of a Courvoisier gall bladder.

A patient who had been jaundice for more than four months was examined with diagnostic ultrasound. Ultrasound examination revealed that the patient had a solid-appearing mass in the region of the gall bladder, in addition to findings diagnostic of obstructive jaundice. A probable mass was also noted in the head of the pancreas. The clinical data and representative echographic pictures are presented to emphasize the point that sludge within the gall bladder is echogenic and appears more solid than cystic on a standard echographic examination.

Aged

Beta-lactamase effect on ampicillin treatment of Haemophilus influenzae B bacteremia and meningitis in infant rats.

Intraperitoneal injections of 250 mg of ampicillin per kg every 6 h for 30 h sterilized the blood and cerebrospinal fluid of infant rats infected with either a beta-lactamase-containing strain of Haemophilus influenzae type b or a strain lacking the enzyme. However, a single injection of 100 mg/kg sterilized the blood and cerebrospinal fluid of significantly fewer of those rats infected with the beta-lactamase-producing strain. The results suggest that resistance of beta-lactamase-containing strains of H. influenzae in vivo may be inoculum dependent, as demonstrated previously in vitro. The infant rat model appears suited for the quantitative delineation of the effect of beta-lactamase on the treatment of H. influenzae bacteremia and meningitis with beta-lactamase antibiotics.

Ampicillin

"Pseudostone" of the gallbladder. Ultrasound findings and case report.

The ultrasonic criteria for the diagnosis of gallbladder calculi are: (1) echo-dense structures which disturb the smooth contour of the posterior border of the gallbladder; (2) sonic shadowing, and (3) echoes from within the gallbladder. Diagnostic confidence increases greatly in cases in which internal echoes, contour irregularities, and sonic shadows have occurred simultaneously. A case is presented in which all three criteria are fulfilled, but which represents an artifact, i.e., "pseudostone." This was confirmed by varying the patient's respiration and showing that the "pseudostone" represented echoes from a loop of bowel which produced a significant impression on the posterior wall of the gallbladder during deep inspiration. The absence of cholelithiasis was confirmed by oral cholecystography.

Cholecystography

Phycomycotic gangrenous cellulitis. A report of two cases and a review of the literature.

Progressive gangrenous cellulitis due to Rhizopus arrhizus following colostomy destroyed the entire abdominal wall of a young woman and caused her death. A similar infection in an 11-year-old kidney transplant recipient was diagnosed more promptly and treated successfully with extensive debridement and amphotericin B. Nine similar cases found in the literature were reviewed. All 11 patients appeared to have had prior tissue injury at the original site of infection, and seven had diabetes mellitus. The disease was initially misdiagnosed in most of the patients, progressed rapidly in eight, and was fatal in four. Phycomycotic gangrenous cellulitis should be included in the differential diagnosis of progressive necrotizing lesions of the skin, especially in diabetic patients, but it can be identified promptly only by histologic examination of the infected tissue. Urgent radical excision and amphotericin therapy are recommended.

Abdominal Muscles

Inter- and intralaboratory variability in antibiotic susceptibility tests with Pseudomonas aeruginosa and Enterobacteriaceae.

A two-phase collaboratice study was designed for definition of the extent to which results of disk diffusion tests can be reproduced. Two currently recommended techniques, the Kirby-Bauer method and the agar overlay method, were used. Of special concern were tests of Pseudomonas aeruginosa with moderate susceptibility to carbenicillin; gentamicin, tobramycin, polymyxin B, and colistin were also tested with P. aeruginosa as well as with Klebsiella pneumoniae, Escherichia coli, and Proteus species. The agar overlay method tended to give zones that were somewhat smaller than those given by the Kirby-Bauer method. Both disk methods demonstrated an excellent degree of reproducibility, being at least as reproducible as the standard agar dilution technique for measurement of minimal inhibitory concentrations. Slight changes in carbenicillin disk potency affected the zones of inhibition around P. aeruginosa more than those around susceptible E. coli. This fact suggests that a standard strain of P. aeruginosa would be advantageous for quality control of carbenicillin disk tests.

Carbenicillin

Ampicillin-resistant Haemophilus influenzae type B possessing a TEM-type beta-lactamase but little permeability barrier to ampicillin.

Ampicillin-resistant Haemophilus influenzae type B have been reported only during the past year. Five clinical isolates from the U.S. and Germany all had the TEM-type beta-lactamase which is known to be transferred widely among other gram-negative bacilli. Unlike those bacilli, however, the H. influenzae cell had very little barrier to entry of penicillins. This greater permeability of the H. influenzae cell to penicillins appeared to reduce the protective effect of its beta-lactamase, in that acquisition of the TEM-type beta-lactamase increased levels of resistance to penicillins much less for individual cells of H. influenzae than for those of Escherichia coli. Large inocula of either species appeared highly resistant. The unusually low level of resistance of individual cells of H. influenzae containing the TEM-type beta-lactamase may have delayed their emergence or recognition, and has unresolved clinical implications.

Amidohydrolases

Listeroisis in immunosuppressed patients. A cluster of eight cases.

Bactermia due to listeria monocytogenes developed in eight patients who were receiving immunosuppresive medications during a 15 month period at one hospital. Seven survived. Meningitis was documented in only the four who received kidney transplants. Their neurologic signs were minimal, indicating a need to treat any immunosuppressed patient with Listeria bacteremia for meningitis. During this period the incidence of Listeria bactermia in immunosuppressed patients greatly exceeded that previously observed in this hospital or reported elsewhere, but the incidence of infection with other opportunistic agents was not increased. As with previously decreased listeria outbreaks in nonimmunosuppressed patients, no source or mechanism of spread could be identified. Thus, disease due to L. monocytogenes may occur focally among immunosuppressed populations, a pattern which also appears to be emerging for other opportunistic agents. A patient's exposure to different opportunistic agents may be as important as the kind of immunosuppressive therapy he recieves in determining which opportunistic infection he will acquire or even whether any infection will occur.

Adolescent