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Biomedical subjects

C M Kunin

Publications and source records attributed to C M Kunin.

At least 19 recordsLinked to original sources

The association between the use of urinary catheters and morbidity and mortality among elderly patients in nursing homes.

To determine whether the use of urinary catheters in elderly patients in nursing homes has an independent effect on morbidity and mortality, the authors conducted a 1-year prospective study among 1,540 patients in a stratified random sample of nursing homes. Patient mortality was assessed at 1 year in relation to the presence or absence of a catheter at entry to the study, acquisition of a catheter, and the proportion of nursing home days spent catheterized during the study year. The independent association of catheter use with mortality was assessed by logistic regression analysis adjusted for age, activities of daily living, mental status, skin condition (decubitus ulcers), and 20 medical diagnoses. The effect of catheterization on hospitalization, use of systemic antimicrobial drugs, and mortality was also examined by matched pairs analysis. At entry, 10.5% of patients had catheters, and they tended to remain catheterized during most of the study year. An additional 10% were catheterized during the year. The following factors were found to have a significant independent association with mortality: urinary catheters, age, mental status or activities of daily living, cancer, cardiac disease, diabetes, and skin condition. There was a stepwise increase in mortality with duration of catheterization. Patients who were catheterized for 76% or more of their days in the nursing home were three times more likely to die within a year. The number of hospitalizations, duration of hospitalization, and use of antimicrobial drugs were all three times greater among catheterized patients.

Activities of Daily Living

General guidelines for the clinical evaluation of anti-infective drug products. Infectious Diseases Society of America and the Food and Drug Administration.

This document provides new general guidelines for the design and execution of studies evaluating anti-infective drugs for the prevention or treatment of infectious diseases. The first step in evaluation is the determination of in vitro microbial susceptibility. Next, studies are conducted in animals. Several animal models provide information useful in the prediction of appropriate dosing and activity in humans. If the results of these studies are favorable, staged clinical trials are then conducted. These guidelines reflect changes in the practice of medicine, dealing with topics such as the switch from parenteral to oral drug administration during a course of therapy, treatment in settings other than acute-care hospitals, and the use of alternative comparison drugs for the study of indications or dosing schedules not covered by the product label. Because further changes in practice are anticipated, the present guidelines will need to be updated and revised periodically.

Animals

Growth of Escherichia coli in human urine: role of salt tolerance and accumulation of glycine betaine.

Glycine betaine is a powerful osmoprotectant molecule present in the inner medulla of the kidney and excreted into urine. It may be responsible for the ability of Escherichia coli to grow in hypertonic urine. Also, strains of E. coli that cause urinary tract infections may be more salt-tolerant than strains from other sites. To explore these questions, 301 isolates from blood, urine, or stool and 12 representative enteric strains were examined. Tolerance varied from 0.1 to 0.7 M NaCl (median, 0.5) in minimal medium. There were no significant differences in salt tolerance by site of isolation. A salt-sensitive enteric strain that responded poorly to glycine betaine and mutant strains lacking the ability to synthesize or transport glycine betaine did not grow well in hypertonic urine. Accumulation of glycine betaine appears to be a mechanism by which E. coli can adapt to external osmotic forces and grow in hypertonic urine.

Betaine

Effect of hydrogen peroxide on growth of Candida, Cryptococcus, and other yeasts in simulated blood culture bottles.

The addition of hydrogen peroxide to blood contained in liquid culture medium increased the dissolved-O2 partial pressure in direct proportion to the volume injected. The effect of hydrogen peroxide on the growth of subcultured clinical isolates of Candida albicans, Cryptococcus neoformans, Torulopsis glabrata, and other yeasts and on the growth of blood culture isolates of representative pathogenic bacteria was compared with its effect on their growth in vented and unvented stationary bottles. C. albicans and C. neoformans grew significantly better in bottles to which hydrogen peroxide had been added than in vented or unvented bottles. The advantage of hydrogen peroxide over venting was most marked with several slowly growing strains. Similar results were obtained in shaker cultures with strains of C. albicans which were inoculated directly from positive blood cultures. The effect of hydrogen peroxide tended to diminish during serial passage. T. glabrata grew less well when hydrogen peroxide was added, perhaps because of the absence of oxidase. The growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis was not significantly inhibited or augmented by the addition of hydrogen peroxide. The growth of Escherichia coli was inhibited slightly. The value of the addition of hydrogen peroxide to blood cultures to improve the isolation of yeasts needs to be established by a clinical trial which would compare this method with established methods.

Blood

Survey on use of antimicrobial agents and bacterial resistance in Huashan Hospital.

A cross-section study was carried out to assess the general patterns in use of antimicrobial agents and the trends of bacterial resistance in Huashan Hospital. Of 2,400 patients whose charts were reviewed, 61% were given such drugs. 3,596 antibiotic courses were prescribed. Gentamicin was most frequently used. Results of the susceptibility test of 320 bacterial strains showed a high percentage of resistance against gentamicin, ampicillin, and chloramphenicol. Our findings suggest that antibiotic policies in the hospital need reappraising.

Adolescent

Effect of NaCl-induced osmotic stress on intracellular concentrations of glycine betaine and potassium in Escherichia coli, Enterococcus faecalis, and staphylococci.

Staphylococci are more salt tolerant than are enterococci or Escherichia coli. They have a more rigid cell wall and higher internal turgor pressure. The mechanisms of NaCl-induced osmotic tolerance among these bacteria were examined by determining the generation of osmoprotective activity of cellular extracts and intracellular concentrations of glycine betaine and potassium (K+) in response to graded amounts of NaCl. Staphylococci as well as E. coli were shown to require choline or glycine betaine to achieve maximal salt tolerance. In response to 0.9 mol/L NaCl, E. coli exhibited a marked increase in osmoprotective activity, a 168-fold rise in glycine betaine, and a 2.3-fold rise in K+. Enterococcus faealis exhibited a small increase in osmoprotective activity, a 9.3-fold increase in glycine betaine, and a twofold increase in K+. In contrast, strains of Staphylococcus aureus, S. epidermidis, and S. saprophyticus were found to have considerably greater osmoprotective activity, glycine betaine, and K+ than other organisms, even in the absence of external osmotic stress. Glycine betaine rose in some strains, but K+ remained virtually unchanged as the concentration of NaCl was increased. The high concentrations of glycine betaine and K+ in staphylococci, even in the absence of osmotic stress, may explain in part their remarkable salt tolerance and high turgor pressure.

Betaine

Natural history of "lower" urinary tract infections.

Our current knowledge of the long-term outcome of uncomplicated urinary tract infections in women is based on a re-evaluation of the criteria for defining pyelonephritis at autopsy, careful description of the causes of renal disease among patients entering dialysis and transplant programs, long term observation of patients, and epidemiologic studies which have attempted to determine the association of bacteriuria with mortality. The weight of the evidence favors the conclusion that although urinary tract infections can produce severe impairment of renal function, this is rare in the absence of a major predisposing factor such as obstruction, calculus, reflux, abnormalities of the voiding mechanism or diabetes. The predisposing lesions, however, may go undetected until heralded by episodes of acute pyelonephritis or by renal failure. Unfortunately, urinary tract infections are so common that it is difficult to distinguish the population at greatest risk. The possible role of renal damage produced by autoimmune mechanisms following infection needs continued study.

Adult

The implications for Europe of revised FDA guidelines for clinical trials with anti-infective agents.

This article summarizes the current collaborative effort between the US Food und Drug Administration and the Infectious Diseases Society of America for the purpose of generating new General and Disease/Organism Specific Guidelines for the evaluation of anti-infective agents. Examples of proposed changes from draft documents are presented. The final documents may assist European colleagues in their efforts to establish a standardized new drug registration process by 1992. An area of mutual interest is the acceptability of safety and efficacy data from international clinical trials. In the interest of human and financial economies, both US and European Guidelines need to clarify the conditions, or criteria, for the conduct of valid 'off-shore' clinical trials.

Anti-Infective Agents

Purchase of antibiotics without prescription in Manila, the Philippines. Inappropriate choices and doses.

The purchase of antimicrobial agents in drugstores in a district in Manila. The Philippines was examined in order to determine how these agents might be used. Most antimicrobial agents are imported as bulk products and repackaged by a large number of small firms into 1491 different preparations including 206 marketed as combinations with other drugs. Antimicrobial agents accounted for 20.1% of all drug purchases. Purchases were made without prescription in 66.3% of 1608 transactions. Most of these were aminopenicillins or penicillins G or V (40.0%). The most common perceived indications were respiratory tract infections (20.2%), tuberculosis (8.8%), "prophylaxis" (8.6%) and gastrointestinal infection (8.3%). Almost 90% of purchases were for 10 or less capsules or tablets. The median number of units purchased was 3. Customers with written prescriptions purchased a mean of 8 while those who self-prescribed purchased a mean of 4 units (p = less than 0.05). We believe that these practices can provide only limited clinical efficacy and should favor emergence of resistant bacteria.

Anti-Bacterial Agents

Blockage of urinary catheters: role of microorganisms and constituents of the urine on formation of encrustations.

Long-term indwelling urinary catheters may become blocked in some patients by formation of encrustations made up of aggregated struvite crystals while other patients rarely develop blocked catheters. We have designated these groups as "blockers", "intermediates" or "non-blockers". To further understand this phenomenon we followed 32 catheterized elderly women in a nursing home. Catheters were changed six times at 2 week intervals. Patients tended to remain as "blockers", "intermediates" or "non-blockers" consistently over time. There were no significant differences in use of antibiotics, clinical manifestations of urinary infection or fever among the groups. "Blockers" were significantly more often colonized with Proteus mirabilis and Providencia stuartii than "non-blockers", and significantly less often with Klebsiella pneumoniae. However, there was no evidence of interference among the organisms. "Blockers" excreted a significantly more alkaline urine, and lesser amounts of magnesium, urea and phosphate in their urine. Two "blockers" in whom Proteus sp. were eliminated by coincidental antimicrobial therapy converted to "non-blockers". These findings support the concept that "blockers" are patients who have prolonged colonization with urease producing Proteus mirabilis and Providencia stuartii.

Aged

Natural history of bacteriuria in schoolgirls. A long-term case-control study.

To define better the natural history of bacteriuria in females, we followed 60 schoolgirls with bacteriuria and 38 matched controls for periods ranging from nine to 18 years. Among the schoolgirls with bacteriuria (greater than or equal to 10(5) organisms per milliliter in two or more consecutive cultures), reflux was repaired in five, nephrectomy was performed in two, and reduced inulin clearance was noted in one subject with atrophic pyelonephritis. Serum creatinine was slightly higher in cases than in controls. Renal scars or caliectasis occurred in 16 cases but in none of the controls. Blood pressure was similar in both groups. Episodes of bacteriuria in cases and controls were, respectively: five or more episodes, 21.7 and 2.6 per cent; and episodes during pregnancy, 63.8 and 26.7 per cent. Seven children of the cases but none of the children of controls showed urinary-tract infections. Bacteriuria among schoolgirls defines a group at great risk of recurrent symptomatic infections and renal scars and at low risk of reduced renal function.

Acute Disease

Oral neomycin dosage schedules for suppression of ammonia production by bowel flora.

To better define a minimal but optimal dose of oral neomycin to suppress ammonia production by bowel flora, several dosage regimens were examined in normal healthy volunteers. Fecal urease activity was quantitatively determined and was used as an indirect measure of intrinsic ammonia production by bowel flora. Large doses of neomycin were found to exert inhibition of fecal urease for many days. There was considerable variation in enzymatic activity among subjects even after adjustments were made for protein content of the stool. Depending on the dose, there was a 1- to 3-day lag in neomycin effect on stool urease activity and several days of continued effect. The most effective regimen of those studied was a loading dose of 6 g of neomycin given in three divided doses on day 1, followed by 1 g twice daily.

Adult