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Biomedical subjects

T F O'Brien

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

At least 73 records · Page 4Linked to original sources

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

Computer surveillance of shifts in the gross patient flora during hospitalization.

Data accumulating routinely in a hospital microbiology laboratory were computer-plotted according to the number of days the patient had been in the hospital when each culture was obtained. The rate at which patients were cultured fell slightly during hospitalization, while the rate at which isolates were obtained from them increased gradually. For some species, such as Escherichia coli or Staphylococcus aureus, isolation rates changed little during hospitalization. They rose as much as sevenfold for other species, such as Pseudomonas aeruginosa or Serratia marcescens, or for a particular antibiotype of Klebsiella pneumoniae while it was an endemic nosocomial problem. These differences persisted after deletion of repeat isolates from the same patient. They appeared to reflect general shifts in composition of patient flora during hospitalization. These shifts paralleled shifts in infecting flora as represented by similar plots of isolates from blood cultures.

Bacteria

Streptomycin dependence in Escherichia coli: effects of antibiotic deprivation on ribosomes.

The inhibition of cell division and the ultimate loss of viability after removal of streptomycin from growing cultures of streptomycin-dependent bacteria are not the result of "unbalanced growth" or of the breakdown of ribosomes. The streptomycin-dependent strain of Escherichia coli K-12 studied continued to synthesize ribonucleic acid (RNA) and protein during streptomycin starvation. There was no evidence of a gross imbalance in the ratio of RNA to protein synthesized or of selective degradation of either protein or RNA. Using the sedimentation of subunits in sucrose as the criterion, normal ribosomes were synthesized even after 18 h of streptomycin deprivation, although the rates of appearance of mature 30S and 50S subunits decreased with time of deprivation. Once formed, these ribosomes appeared stable, as did those synthesized before the onset of starvation. Ribosomes isolated from starved dependent cells were as "functional" as ribosomes from cells grown with streptomycin in their capacity to bind aminoacyl-transfer RNA in response to polyuridylic acid or natural messenger RNA to interconvert between active and inactive transfer RNA binding states, and to synthesize proteins in cell-free systems. The effects are consistent with an impaired rate of synthesis of ribosomal components or assembly of ribosomes resulting in a continually diminishing rate of protein synthesis. The effect on cell division may be the result of a decreased rate of protein synthesis in general and the requirement for a specific protein(s) in particular.

Escherichia coli

Inhibitory effects of citrates in the determination of trace amounts of penicillin.

In the microbiological assay for the determination of trace amounts of penicillin, it has been shown that sodium citrate and penicillin act synergistically against Sarcina lutea. The inhibitory action of citrate appears to involve a sequestering of divalent cations essential to the growth of the organism as shown by minimal inhibitory concentration and agar diffusion studies. The addition of calcium or magnesium to broth or agar at various concentrations overcomes this inhibition, and 0.02 M magnesium was found to be the most effective concentration. On agar supplemented with magnesium chloride, penicillin dose-response curves with and without citrate present were practically superimposable, and larger inhibition zones against a greater amount to total growth resulted in improved assay susceptibility and an interference-free method. Misleading results can be obtained when pharmaceutical products containing citrates are tested by conventional methods for penicillin cross-contamination.

Biological Assay

Characterization and prevalence of the different mechanisms of resistance to beta-lactam antibiotics in clinical isolates of Escherichia coli.

A survey of clinical isolates from a hospital laboratory showed that Escherichia coli could be grouped into three classes of beta-lactam-antibiotic resistance by results of routine susceptibility testing to ampicillin, cephalothin, and carbenicillin. E. coli highly resistant to ampicillin and carbenicillin but not to cephalothin (class I) were found to have one of two levels of R factor-mediated, periplasmic-beta-lactamase which resembled R(TEM) and was located behind a permeability barrier to penicillins but not to cephalosporins. This permeability barrier appeared to act synergistically with the beta-lactamase in producing high levels of resistance to penicillins. E. coli highly resistant to ampicillin and cephalothin but not carbenicillin (class II) were found to have a beta-lactamase with predominantly cephalosporinase activity which was neither transferable nor releasable by osmotic shock. E. coli moderately resistant to one or to all three of these antibiotics (class III) were found to have low levels of different beta-lactamases including a transferable beta-lactamase which resembled R(1818). Thus, different mechanisms producing resistance to beta-lactam antibiotics could be deduced from the patterns of resistance to ampicillin, cephalothin, and carbenicillin found on routine susceptibility testing. E. coli of class I were much more prevalent than the other classes and the proportion of E. coli that were class I increased with duration of patient hospitalization. The incidence of class I E. coli rose only slightly over the past 7 years and that of class II E. coli remained constant despite increased usage of both cephalothin and ampicillin. These observations emphasize that the properties of the apparently limited number of individual resistance mechanisms that exist in a bacterial flora, such as their genetic mobility and linkages and the spectrum of their antibiotic inactivating enzymes and permeability barriers, may govern the effect that usage of an antibiotic has upon the prevalence of resistance to it and to other antibiotics.

Amidohydrolases