A risk management checklist. For academic and complex community medical centers.
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Academic Medical Centers↗
Biomedical subjects
T F O'Brien
Publications and source records attributed to T F O'Brien.
Broad-spectrum, transmissible beta-lactamases.
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Bacteria↗
Glycoconjugate boundaries during early postnatal development of the neostriatal mosaic.
The dispositions of galactosyl-containing glycoconjugates were studied during postnatal development of the caudate putamen in mice. The binding of the lectin peanut agglutinin, which has an affinity for galactosyl B-1,3 N-acetylgalactosamine residues, was compared to acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity in the immature and adult neostriatum. The binding of peanut agglutinin conjugated to horseradish peroxidase, in sections that were processed for peroxidase histochemistry, was extremely pronounced in the neostriatum through the first postnatal week and constituted ringlike or polygonally shaped structures, which, overall, produced a variegated mosaic. These structures consist of outer rims of dense lectin-associated reaction product surrounding lightly labeled centers. Lectin delineations of the neostriatal mosaic are no longer visible in the second postnatal week. When adjacent sections were processed for lectin binding or acetylcholinesterase histochemistry, the dense lectin binding sites represented borders of acetylcholinesterase-rich and -poor zones. The distribution of dense patches of tyrosine hydroxylase immunoreactive fibers and terminals also coincides with the acetylcholinesterase-rich zones during the same times, and thus the glycoconjugate-delineated boundaries can also be directly compared with the distribution of nigrostriatal dopaminergic projections. The findings presented here represent the first demonstration of a probe that recognizes apparent borders of neostriatal compartments during a limited period of development. They are consistent with previous observations made on transient glycoconjugate "hidden boundaries" during development of other central nervous system structures, including the somatosensory cortical barrel field, and thalamic and brainstem nuclei (Cooper and Steindler, '86a,b; Steindler and Cooper, in press). In those studies, glia were shown to be the major source of glycoconjugate-associated patterns, and thus, glia and glycoconjugates that they synthesize during pattern formation events may be involved in the formation and stabilization of neurochemically distinct components of the neostriatal mosaic.
Acetylcholinesterase↗
Functional and structural map of pLST1000: a multiresistance plasmid widely distributed in Enterobacteriaceae.
pLST1000, an 80-kb plasmid found in Enterobacteriaceae in North and South America, harbors the aadB and several other resistance genes. We suggested earlier that, because of its widespread distribution, pLST1000 could act as a carrier plasmid, bringing the aadB gene to new locations. This paper presents the restriction enzyme recognition site and functional map of the plasmid. The resistance genes lie in a discreet region. The aadB and aadA genes form an operon with the aadB gene promoter proximal. This operon is flanked by bla-TEM and bla-OXA2 genes, the former located in a functional Tn3-like transposon. This arrangement is similar to that of relatives of the transposon TN21, where additional resistance genes are precisely inserted in recombinational "hot spot" sequences that flank the aadA gene. We were not able to demonstrate transposition of the aadB gene in Escherichia coli. A sul gene and mer operon lie beyond the bla-OXA2 gene. The transfer genes form a single region, defined by insertions of Tn5-132 that give the Tra- phenotype.
Drug Resistance, Microbial↗
Abnormal glial and glycoconjugate dispositions in the somatosensory cortical barrel field of the early postnatal reeler mutant mouse.
During early postnatal development in reeler mutant mice, lectin binding delineates prospective abnormal barrels as they will appear in the adult mutant somatosensory cortex. Glial fibers also may be more condensed within fascicles in developing reeler barrels. These fibers also appear to be misaligned, coursing predominantly in the tangential plane within the abnormal reeler barrel sides as opposed to having a radial orientation as seen in normal mouse barrels. The thalamic barreloid complex, however, reveals a disposition of glycoconjugates that is completely normal in reeler. Thus, there are anomalies in glia and associated glycoconjugates during mainly cortical development in the reeler mutant mouse that might be related to the primary action of the abnormal gene.
Animals↗
Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy.
Minimal inhibitory concentrations of cephalosporins for a strain of Salmonella typhimurium from one patient increased severalfold after starting therapy with cephalexin. The first isolate with increased resistance (S20323) and an earlier, less resistant isolate (S17069) each had a TEM-1 beta-lactamase with similar Vmax and Km values. Intact cells of S20323 grown in a high osmolality medium hydrolyzed cephalosporin substrates much more slowly than did intact cells of S17069 at low substrate concentrations, a result indicating slower diffusion of cephalosporins into S20323. In low osmolality media, S17069 produced both OmpF and OmpC porins; S20323 produced only OmpF porin. In high osmolality media with osmotic activity similar to that in the patient's tissues, synthesis of the OmpF porin was repressed in both strains and left S20323 with undetectably low levels of any porin. The increased beta-lactam resistance in S20323 is apparently a consequence of the loss of the OmpC porin.
Adult↗
Resistance to antibiotics at medical centres in different parts of the world.
The diameters of the zones of inhibition of consecutive clinical isolates around antibiotic susceptibility test discs at medical centres in different parts of the world were computer filed and analysed by a series of programs that evaluate test quality and compare results. Percentages of isolates resistant to ampicillin at 18 centres ranged from 16 to 73 for Escherichia coli and from 3 to 56 for Proteus mirabilis. Percentages resistant to chloramphenicol ranged from 2 to 48 for E. coli, from 5 to 52 for Klebsiella pneumoniae, and from 8 to 67 for Serratia marcescens. Gentamicin resistance did not exceed 4% at any of 18 centres and was less than 1 at 14 of them for isolates of E. coli, while K. pneumoniae showed less than 2% resistance at six centres but averaged 22% at another eight. Multi-resistant isolates were ten-fold more frequent at eight centres than at the remaining six. Too few centres were sampled to characterize individual countries except in the United States where resistance seemed generally less prevalent.
Anti-Bacterial Agents↗
Molecular evolution, species distribution, and clinical consequences of an endemic aminoglycoside resistance plasmid.
During the first 6 years after appearing in one hospital, a 92-kilobase conjugative plasmid, pBWH1, which encoded resistance to chloramphenicol and sulfonamides and determined TEM-1 beta-lactamase and 2''-aminoglycoside nucleotidyltransferase, underwent a variety of molecular changes. It was most prevalent initially in isolates of Klebsiella pneumoniae, then in isolates of Serratia marcescens, and finally, after nearly disappearing, in isolates of Enterobacter cloacae. Evolutionary changes in the plasmid did not account for its shifts in species distribution, since the original molecule was found in isolates of each species. The late resurgence of pBWH1 occurred after a copy of its original molecule entered a distinctive ornithine decarboxylase-negative strain of E. cloacae, new to the hospital. The resulting transconjugant strain, chromosomally resistant to topical silver salts and to cephalosporins, and with the addition of pBWH1-encoded aminoglycoside resistance, spread in the hospital by causing an outbreak of sepsis in the burn unit, where these were commonly used antibacterial agents. Thus, an endemic plasmid became prevalent in a new host species because one of its genes supplemented the fitness of an uncommon strain of the species for a particular clinical niche.
Aminoglycosides↗
Genetic and physical characterization of IncM plasmid pBWH1 and its variance among natural isolates.
We present a genetic and physical characterization of the IncM plasmid pBWH1. A physical map was constructed for the enzymes EcoRI, BamHI, SalI, BglII, HindIII, MstII, and XhoI. A series of deletions and a series of subclones of pBWH1 were constructed and used to determine the locations on this map of the transfer region; the replication region; and the genes determining resistance to beta-lactams, chloramphenicol, the sulfonamides, and gentamicin. We compared 51 different isolates, including isolates which had lost individual antibiotic resistances or the transfer phenotype, and showed that variations occurred in all regions of the plasmid genome. Frequently, correlations could be made between phenotypic variation and variation of the EcoRI fragments which contained the gene determining that phenotype.
Chromosome Mapping↗
Intercontinental spread of a new antibiotic resistance gene on an epidemic plasmid.
Bacteria of different genera isolated at nine medical centers in different parts of the United States and at one center in Venezuela during the first decade of gentamicin usage carried the gentamicin resistance gene 2"-aminoglycoside nucleotidyltransferase on the same transferable plasmid. Such widespread dissemination of a newly observed resistance gene on one plasmid suggests that a new resistance gene may emerge once on a single plasmid, which then carries it to other centers and other plasmids. The resistance gene might, therefore, be contained if detected early.
Bacteria↗
Revisiting the Holy Cross football team hepatitis outbreak (1969) by serological analysis.
Clinical and biochemical data collected during the Holy Cross College football team hepatitis A outbreak in 1969 suggested that 32 team members had icteric hepatitis, 58 had anicteric illness, and only seven were not infected. Using a currently available radioimmunoassay, we tested stored serum samples obtained during the outbreak for IgM antibody to hepatitis A virus (IgM anti-HAV). Only individuals with icteric hepatitis were found to have IgM anti-HAV in serum; those with presumed anicteric illness were shown not to be infected with hepatitis A virus. The attack rate was thus only 34%, not 93% as originally reported, and the incidence of icteric illness in those infected was 100%, not 33%. This serological analysis of a classic outbreak of hepatitis A illustrates the utility and importance of IgM anti-HAV testing in seroepidemiologic investigations of hepatitis outbreaks.
Alanine Transaminase↗
Resistance to antibiotics in clinical isolates of Klebsiella pneumoniae.
The antibiotic resistance of Klebsiella pneumoniae isolates from 12 medical centers worldwide, over a 1- to 6-year period, were tested. Clinical isolates of K. pneumoniae were resistant to ampicillin and carbenicillin. Resistance to other antibiotics was less frequent with isolates of K. pneumoniae from 5 of 6 US centers than with those from 6 centers outside the US. In nearly all of the centers, resistance to sulfamethoxazole-trimethoprim, gentamicin, tobramycin, or chloramphenicol was more frequent in isolates of K. pneumoniae than in those of Escherichia coli, while the reverse was true for resistance to tetracycline. Resistance to multiple antibiotics declined gradually in isolates of K. pneumoniae at one center, but rose abruptly again with dissemination of a new plasmid.
Ampicillin↗
Trimethoprim resistance in multiple genera of Enterobacteriaceae at a U.S. hospital: spread of the type II dihydrofolate reductase gene by a single plasmid.
The percentage of clinical isolates of several species of Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, resistant to trimethoprim (TMPR) has increased gradually at the Brigham and Women's Hospital (Boston) in recent years. Thirty-seven of 42 TMPR isolates from six species of gram-negative bacilli conjugally transferred TMP resistance to K12 E. coli. beta-Lactam resistance cotransferred from 21 of the 37 donors, and sulfamethoxazole (SMZ) resistance cotransferred from five of the 37 donors. Plasmids that encoded TMP resistance either alone or with SMZ resistance had a molecular size of approximately 52.5 kilobases, with identical restriction endonuclease-generated "fingerprints." Plasmids encoding beta-lactam-mediated resistance (beta R) were approximately four kilobases larger and had fragment patterns that were identical for all of the TMPR/beta R plasmids tested and had many restriction endonuclease-generated bands in common with TMPR plasmids. Radiolabeled dihydrofolate reductase (DHFR) probes identified the type II DHFR as the determinant of TMP resistance. In contrast with reports from Europe, TMP resistance in multiple species of Enterobacteriaceae was found to be spread in one hospital by a single, stable conjugative plasmid that has a wide host range and encodes the type II DHFR gene.
Conjugation, Genetic↗
Urinary tract infections in an American rehabilitation hospital.
In order to gain a better understanding of urinary tract infection in a rehabilitation hospital, the hospital courses of 119 consecutively admitted patients were studied. Bacteriuria on admission and subsequent incidence of urinary tract infection occurred chiefly among those patients with diagnoses involving peripheral vascular disease and low level of function (Barthel Index) on admission assessment. Females and diabetics among that group were particularly at risk. It was concluded that by using admission screening for detection of bacteriuria and level of function, the members of the high risk group could be predicted, and early urology consultation for bladder training programmes could be focused on those patients who might derive the most benefit.
Aged↗
Diagnostic microbiology laboratory susceptibility test results discriminate distinctive antibiotic resistance plasmids.
The sizes of the zones of inhibition around routinely tested antibiotic disks classified gentamicin-resistant isolates of Klebsiella pneumoniae from one hospital into four major antibiotype classes. From each isolate of the prevalent class (A1), two plasmids could be transferred conjugally. One carried genes for resistance to tetracycline, sulfonamides, and chloramphenicol, and for the SHV beta lactamase. The other carried genes for two aminoglycoside-inactivating enzymes, APH (3')-I and AAC (3)-III, for the TEM 1 beta lactamase, and for resistance to sulfonamides. Transconjugants of either plasmid from any A1 isolate yielded the same DNA fragments after restriction endonuclease digestion, but the two plasmids had no fragments in common. Fragments or genes from either plasmid were variously combined or lacking in plasmids from variant isolates (A2, A3, and A4). Plasmids transferable from isolates of classes B and C shared no common DNA restriction fragments with each other or with either plasmid from Class A. Fragments and genes of the plasmids from C isolates, however, were identical with those of a plasmid endemic in a nearby hospital. Routine monitoring by diagnostic microbiology laboratories of distinctive antibiotypes and of the plasmids that produce them would aid infection control and antibiotic usage policy.
Anti-Bacterial Agents↗
Infection control surveillance in a rehabilitation hospital.
Infection control surveillance in a rehabitation setting is essential to quality assurance because of the high number of infection risk factors found in this patient population. These factors include longer length of stay, high incidence of urinary tract instrumentation, and high incidence of skin lesions, including decubital and stump wounds. A surveillance process is described which offers timely access to each infected patient's diagnosis, treatment, and follow-up, and results in simplified hospital-wide antibiotic monitoring. Quality assurance problems identified through this surveillance plan involved specimen collecting and reporting errors, nursing-procedure inadequacies, and organism misidentification. These and other examples illustrate the distinctive role an infection control program can play in quality monitoring and problem solving in a rehabilitation hospital.
Cross Infection↗
Sarcoidosis presenting as biliary cirrhosis: treatment with chlorambucil.
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Chlorambucil↗