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Biomedical subjects

R H Eng

Publications and source records attributed to R H Eng.

At least 19 recordsLinked to original sources

Accuracy of disincorporation for identification of vascular graft infection.

OBJECTIVE: The presence or absence of prosthetic graft incorporation with surrounding tissue was assessed relative to bacterial culture results, using enhanced microbiologic culture techniques. DESIGN: Criterion standard. SETTING: University and Veterans Affairs hospital. PATIENTS: Prosthetic samples were removed from 113 aortofemoral, extra-anatomic, infrainguinal, and hemoaccess sites at the time of vascular reoperative surgery. Harvested grafts were sonicated. Density of organisms was determined by quantitative culture. MAIN OUTCOME MEASURES: The culture result was predicted from the status of prosthetic incorporation or disincorporation as determined at surgery. For purposes of this study, any bacterial growth represented graft infection. RESULTS: Cultures positive for bacteria were obtained from 31 sites; cultures with no growth, from 82. Thirty-one of the 113 sites were disincorporated, of which 23 yielded cultures positive for bacteria, and eight, no growth. The remaining 82 sites were well incorporated, of which 74 yielded cultures negative for bacteria, and eight, bacterial growth. Sixteen (14%) incorrect predictions were noted. The concurrence of disincorporation and a culture positive for bacteria relative to all culture-positive grafts (sensitivity) was 74%. The concurrence of incorporation and cultures negative for bacteria relative to all culture-negative grafts (specificity) was 90% in prostheses implanted for longer than 2 weeks; in prostheses implanted for longer than 12 weeks, specificity was 97%. CONCLUSIONS: The surgical finding of incorporation or disincorporation accurately predicted the culture result in 89% of the sites. Disincorporation correlated with presence of bacteria in 71%; incorporation reliably excluded the presence of bacteria in 97%.

Aorta

Colonization pattern of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Vancomycin-resistant Enterococcus faecium is increasingly recognized as a serious problem by hospital epidemiologists. Understanding its colonization patterns may help in designing strategies to control its nosocomial spread in the hospital. METHODS: Twenty patients, selected at random, with vancomycin-resistant E. faecium isolated from cultures of various body sites were studied to determine sites of colonization. For 12 of these patients, cultures of environmental surfaces of their rooms and wards were also obtained. RESULTS: Eighteen patients (90%) had vancomycin-resistant E. faecium grown in stool cultures. In five patients (25%), vancomycin-resistant E. faecium was cultured from other sites: groins (four), popliteal fossae (three), mouth (one), and an open wound site (one). Patients with positive cultures from the groins and popliteal fossae also had growth of vancomycin-resistant E. faecium in cultures of diarrhea soiling those sites. No patients had the organism isolated from their nares. Vancomycin-resistant E. faecium grew in cultures obtained from bedside stand tables, over-bed tables, used linen, and bedside rails. CONCLUSIONS: In the 20 patients studied, colonization of vancomycin-resistant E. faecium was limited chiefly to the enteric tract. Absence of colonization of such a secluded area with poor antibiotic penetrability as the nares is encouraging. In our study, vancomycin-resistant E. faecium was isolated from various environmental surfaces from the rooms and wards of patients with vancomycin-resistant E. faecium in their stools.

Administration, Oral

Enteric eradication of vancomycin-resistant Enterococcus faecium with oral bacitracin.

The emergence of vancomycin-resistant Enterococcus faecium (VREF) has produced a therapeutic dilemma. The colonization of the intestinal tract with VREF may predispose patients to infections by this organism and may contribute to its nosocomial spread. It is reasonable to attempt to eradicate VREF from colonized patients. The optimal regimen, however, is unknown and this study was designed to evaluate the efficacy of oral regimens of vancomycin and bacitracin for the elimination of VREF from the enteric tract. Enterococcal isolates were tested for susceptibilities to vancomycin, bacitracin, and ampicillin with median minimum inhibitory concentrations of > 512 micrograms/ml, 10 units/ml, and 128 micrograms/ml, respectively. All patients were given an initial trial of oral vancomycin 125 mg every 6 h for 10 days. Those who failed oral vancomycin were then given oral bacitracin 25,000 units every 6 h for 10 days due to its favorable in vitro activity. VREF was eradicated from the stools of 42% of patients (eight of 19) receiving oral vancomycin as compared with all eight patients receiving oral bacitracin (P < 0.01). The organism recurred in two bacitracin patients (25%) 8 and 20 days after completion of therapy. Whether prior vancomycin therapy predisposed patients to colonization by VREF was also examined. Ten (53%) of 19 patients had received prior vancomycin therapy before isolation of VREF from the stool. Our data suggest that oral bacitracin may be an effective alternative to commercially available oral vancomycin for the eradication of VREF from the enteric tract.

Administration, Oral

Optimal method for culturing vascular prosthetic grafts.

Vascular prosthetic infection may be underrecognized when identified by standard culture techniques. Improved microbiologic methodology may enhance detection of bacteria in prosthetic graft specimens, and thus may alter clinical decisions. Quantitative culture techniques were employed to compare three methods of enhancing bacterial recovery from Dacron graft cylinders seeded with commonly encountered bacterial pathogens. Methods included: (1) ultrasonic bath treatment, (2) direct ultrasonic disruption, and (3) agitation on a Vortex mixer. Ultrasonic bath treatment released bacteria with colony counts that were consistently greater by 1 log than direct ultrasonic disruption and Vortex agitation. Direct ultrasonic disruption at high energy levels selectively killed gram-negative bacteria by as much as a 4 log decrease in viable organisms. Agitation (Vortex mixing) of the specimen produced the lowest counts among the three methods tested. These data would indicate that a 5-min ultrasonic bath treatment was the optimal method of preparation of vascular prostheses for bacterial culture.

Bacteria

A comparison of antimicrobial activity of ofloxacin, L-ofloxacin, and other oral agents for respiratory pathogens.

The attainable inhibitory ratios (AR) for oral antibiotics were calculated by using literature reports of concentrations attained in respiratory secretions for amoxicillin-clavulanic acid (AMX/CA), ofloxacin (OFL), L-ofloxacin (L-OFL), cefuroxime (CEFU), ciprofloxacin (CIP), and enoxacin (ENO), and using microdilution minimum inhibitory concentration data of these antimicrobials against the common bacterial respiratory pathogens. AR of each antibiotic against the pathogens was expressed as multiples of the MICs achieved at the respiratory site. Bacteria tested included Staphylococcus aureus, group-A and group-B streptococci, Viridans streptococci, Streptococcus pneumoniae, Brahamella catarrhalis, Klebsiella pneumoniae, Eikenella corrodens, Haemophilus influenzae, H. parainfluenzae, Pseudomonas aeruginosa, and Legionella pneumophila. The antimicrobials with the narrowest spectrum of activity were amoxicillin-clavulanic acid and cefuroxime which had high attainable inhibitory ratios only against Gram-positive cocci. Ofloxacin and L-oflaxacin were among the quinolones with the highest overall ARs against respiratory pathogen, including, L. pneumophila, H. influenzae, and B. catarrhalis. All agents showed no, or inadequately low ARs for P. aeruginosa.

Administration, Oral

Fungemia observations of peripheral tissue clearance in humans.

Patients with fungemia, mainly due to Candida albicans, had cultures repeated from arterial and venous sites to determine yeast cell clearance during fungemia. Of the 48 patients, 37 had repeat positive cultures (36 arterial and venous samples; one venous culture). Additionally, 24 patients had arterial and venous samples cultured quantitatively. An average of 9.1 colony forming units (CFU) ml-1 was isolated from arterial samples and 5.5 CFU ml-1 from venous samples (60% of arterial, P < 0.01). This suggest that arterial fungal densities exceed venous densities and that peripheral tissues clear 40% of yeasts.

Arteries

Involvement of Gardnerella vaginalis in urinary tract infections in men.

Fifteen male patients from whose urine samples Gardnerella vaginalis was isolated (clinical incidence of 0.1%) were evaluated for clinical signs and symptoms of urinary tract infection and modality of acquisition of the organism. Ten of 15 (67%) patients were symptomatic or had signs of inflammation as manifested by an increased number of urinary neutrophils. One patient had two bouts of infection caused by this organism which required two courses of antibiotic therapy. Colonies of diphtheroidlike organisms found in urine cultures should not be ignored as insignificant but should be further investigated to determine whether G. vaginalis is present.

Adult

Escherichia coli resistant to ampicillin/sulbactam.

Escherichia coli strains resistant to ampicillin/sulbactam from hospitals in 4 different geographic locations were examined with respect to type and amount of beta-lactamase produced. A total of 5 strains was examined from each region. The isoelectric points of all of the involved beta-lactamases were 5.4, corresponding to TEM-1. Km and Vmax values of the beta-lactamases among the clinical isolates resembled those from the control TEM-1 strain. In an 18-hour broth culture the highly resistant isolates produced 3 times more beta-lactamase as compared to the ampicillin/sulbactam-susceptible isolates. However, the highly resistant strains contained approximately the same amount of plasmid DNA (size of > 6,500 bp) as the susceptible isolates. In transformation experiments, both the resistance and the degree of resistance appeared to have been transferable by plasmids. The mechanism for resistance is likely to be a baseline overproduction of TEM-1 beta-lactamase due to either an alteration in the control of gene expression or simply to an increase in the number of copies of the beta-lactamase gene in the plasmids.

Ampicillin

Evaluation of two methods for overcoming the antibiotic carry-over effect.

The antibiotic carry-over effect occurs when antibiotic transferred onto the agar plate with the subcultured aliquot is sufficient to inhibit the growth of viable bacteria, and results in a falsely low MBC. This phenomenon was eliminated by widely streaking the transferred aliquot over at least one half of a 100 mm agar plate or by centrifugation and resuspension of the organisms in non-antibiotic-containing media prior to plating. Both methods require more effort than the current method of MBC determination, but can be performed in clinical laboratories and are thus highly recommended in the testing of organisms from endocarditis and meningitis patients.

Centrifugation

An in-vitro and in-vivo comparison of the activity of beta-lactamase inhibitor combinations with imipenem and cephalosporins against Escherichia coli producing TEM-1 or TEM-2 beta-lactamase.

Reference strains of Escherichia coli (ampicillin-susceptible and -resistant ATCC strains, and known TEM-1 and TEM-2 beta-lactamase producers) were tested in vitro and in the in-vivo mouse thigh infection model against four beta-lactamase inhibitor compounds (BICs: amoxycillin/clavulanic acid, ampicillin/sulbactam, ticarcillin/clavulanic acid, and piperacillin/tazobactam), selected cephalosporins, and imipenem. The ATCC strains (ampicillin-susceptible and -resistant) were susceptible to the BICs in disc and MIC tests. Three or more logs of killing were observed at the NCCLS breakpoint concentrations. However, the TEM-1 and TEM-2 producers were resistant in disc tests to ampicillin/sulbactam and amoxycillin/clavulanic acid, and showed intermediate susceptibility to ticarcillin/clavulanic acid. MICs were at or near the breakpoint, but bactericidal activity was only noted at the probable breakpoint concentration of piperacillin/tazobactam. Cefoxitin, cefotaxime, cefpirome and imipenem, but not cephalothin, showed greater bactericidal activity and lower MICs for the TEM-producing strains than the BICs. The viable count of the TEM-1 producer was not reduced in the mouse thigh model by ampicillin/sulbactam or amoxycillin/clavulanic acid, but cefpirome and cefotaxime reduced the viable count by approximately three logs. There was a 50% mortality rate in mice receiving the two BICs. The ampicillin-susceptible ATCC strain of E. coli was killed to a similar degree by all agents tested. Overall, the BICs appeared inferior, in both in-vivo and in-vitro tests to selected cephalosporins and imipenem when tested against reference strains of E. coli producing TEM-1 or TEM-2 beta-lactamase. The large inoculum effect and poor bactericidal activity observed with the BICs suggest they could be less effective in certain clinical situations.

Animals

Development of resistance in candida isolates from patients receiving prolonged antifungal therapy.

The impact of prolonged antifungal therapy on the development of resistance was examined in 61 patients with oropharyngeal thrush. Fifty-nine patients had symptomatic human immunodeficiency virus infection, one had lung cancer, and one had metastatic prostate cancer. Cultures of pharyngeal samples from all patients were positive for yeasts and included 57 (93.4%) Candida albicans, 3 (4.9%) Candida glabrata, and 1 (1.6%) Candida krusii. Of 61 patients, 32 (52.5%) were receiving or had recently received antifungal therapy. Clotrimazole was the most commonly prescribed azole, followed by ketoconazole and fluconazole. Two patients had received amphotericin B therapy and one had received flucytosine. The duration of therapy with clotrimazole, ketoconazole, and fluconazole ranged from 3 to 240, 14 to 44, and 7 to 138 days, respectively. There was no overall difference in the susceptibilities of the clinical isolates from treated and untreated patients to amphotericin B, nystatin, flucytosine, clotrimazole, ketoconazole, and fluconazole. A.C. albicans isolate from one patient who had clinically failed on ketoconazole, fluconazole, and amphotericin B was resistant to these drugs. The lack of difference in the susceptibility pattern indicates that clinically significant emergence of resistance does not occur in those patients who receive prolonged antifungal therapy.

Antifungal Agents

Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria.

Antimicrobial agents are most often tested against bacteria in the log phase of multiplication to produce the maximum bactericidal effect. In an infection, bacteria may multiply less optimally. We examined the effects of several classes of antimicrobial agents to determine their actions on gram-positive and gram-negative bacteria during nongrowing and slowly growing phases. Only ciprofloxacin and ofloxacin exhibited bactericidal activity against nongrowing gram-negative bacteria, and no antibiotics were bactericidal (3-order-of-magnitude killing) against Staphylococcus aureus. For the very slowly growing gram-negative bacteria studied, gentamicin (an aminoglycoside), imipenem (a carbapenem), meropenem (a carbapenem), ciprofloxacin (a fluoroquinolone), and ofloxacin (a fluoroquinolone) exhibited up to 5.7 orders of magnitude more killing than piperacillin or cefotaxime. This is in contrast to optimally growing bacteria, in which a wide variety of antibiotic classes produced 99.9% killing. For the gram-positive and gram-negative bacteria we examined, antibiotic killing was greatly dependent on the growth rate. The clinical implications of slow killing by chemotherapeutic agents for established bacterial infections and infections involving foreign bodies are unknown.

4-Quinolones

Epidemiology of ciprofloxacin resistance among patients with methicillin-resistant Staphylococcus aureus.

During the first twelve months after ciprofloxacin was introduced for clinical use at our institution, 65 new patients were found to be either infected or colonized by methicillin-resistant Staphylococcus aureus (MRSA) which were also ciprofloxacin resistant (CR-MRSA). Only 18 of these patients (28%) had been previously exposed to this antibiotic. Nine (50%) of the 18 patients had received ciprofloxacin for treatment for a pathogen other than MRSA. Although the initial cases of colonization or infection with CR-MRSA can be directly related to ciprofloxacin use, many of the subsequent cases of colonization and infection were not the consequence of ciprofloxacin therapy but rather hospital transmission of existing CR-MRSA.

Ciprofloxacin

Imipenem resistance in a case of AIDS with relapsing Pseudomonas meningitis.

We describe an AIDS patient who had a recurrence of Pseudomonas meningitis to illustrate three points. First, the use of sulfamethoxazole-trimethoprim in AIDS patients for prophylaxis of Pneumocystis carinii pneumonia may cause the various body sites to be colonized with resistant species such as P aeruginosa. Second, Pseudomonas meningitis can recur in a patient with AIDS after a month of appropriate therapy. Finally, imipenem is a poor choice for Pseudomonas meningitis, even when alternative therapies appear much less attractive. High doses of imipenem should not be used for fear of seizures, and lower doses only produce resistant organisms in the CSF.

Acquired Immunodeficiency Syndrome

Bioavailability of clindamycin during peritoneal dialysis.

Clindamycin phosphate becomes biologically active only with cleavage of the phosphate ester bond. A rat model was used to examine the amount of biologically active clindamycin attainable in the dialysate and in the blood during peritoneal dialysis. Intravenous administration of 10 mg/kg clindamycin phosphate alone without peritoneal dialysis produced peak blood levels of 15-20 micrograms/ml. With peritoneal dialysis, blood levels of less than 5 micrograms/ml were achieved. When clindamycin phosphate was added to the dialysis fluid at an initial concentration of 10 mg/ml, less than 5 micrograms/ml of the active antibiotic can be detected in the dialysis return fluids. Even in rats with induced peritonitis, less than 15 micrograms/ml could be found in the dialysis returns. With or without peritonitis, less than 5 micrograms/ml of active clindamycin was attained in blood from peritoneal installation alone. The conversion of the ester to the active compound appears to be the major problem. It is recommended that in those clinical situations in which the patient requires peritoneal dialysis, an alternate antimicrobial agent be used in place of clindamycin to avoid infections in the abdominal cavity or the blood while under therapy.

Animals