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Biomedical subjects

R H Eng

Publications and source records attributed to R H Eng.

At least 37 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Norfloxacin versus trimethoprim-sulfamethoxazole in the treatment of urinary tract infections.

In a controlled, randomized trial of 133 patients with proven urinary tract infections (UTIs), significantly more pathogens were found to be susceptible to norfloxacin than to trimethoprim-sulfamethoxazole (TMP-SMZ) (p less than 0.01). Among patients with pathogens susceptible to both drugs, more of those treated with norfloxacin were cured or improved (p = 0.06). When at least one patient variable, i.e., prior history of therapy, was corrected for, this difference became significant (p = 0.03). Norfloxacin eradicated 11 of 13 infections due to Pseudomonas aeruginosa and 6 of 7 due to enterococci. Five patients treated with norfloxacin and two treated with TMP-SMZ had relapses within 6 weeks. Significantly fewer adverse experiences occurred in patients receiving norfloxacin (p less than 0.01).

Adult↗
PubMed1989

Garlic (Allium sativum) in the treatment of experimental cryptococcosis.

An extract of garlic was studied for its efficacy in treatment experimental cryptococcosis in mice. The garlic, given by mouth, appeared to reduce brain cryptococcal populations, although the results obtained were generally inconsistent. Complete eradication of the cryptococci was not achieved and the early beneficial results observed diminished over time.

Animals↗
PubMed1989

In-vitro and in-vivo activity of cefpirome (HR 810) against methicillin-susceptible and -resistant Staphylococcus aureus and Streptococcus faecalis.

With cefpirome (HR 810) the MICs for both methicillin-resistant Staphylococcus aureus (MRSA) and for Streptococcus faecalis were 8.0 mg/l. At 4 x MIC, cefpirome killed MRSA as rapidly as did vancomycin while for enterococci, cefpirome, vancomycin or ampicillin alone were not bactericidal. However, all agents were bactericidal when combined with 2 mg/l of gentamicin, although gentamicin combined with cefpirome showed a smaller decrease in cfu/ml than the combination with ampicillin or vancomycin. A mouse thigh infection model was developed in which the thigh muscle was infected with bacteria and either no therapy or concurrent antibiotic therapy was initiated. On the subsequent day, the entire thigh muscle was quantitatively cultured. In this model, the numbers of enterococci at the infection site at 24 h were reduced by 2.1 logs with no treatment, 2.6 with cefpirome (25 mg/kg/day), 2.8 with ampicillin (150 mg/kg/day), and 2.7 with vancomycin (25 mg/kg/day). For MRSA the reductions were 1.1 logs with no therapy, 2.8 with vancomycin, and 3.0 with cefpirome. The apparent enhanced in-vivo activity of cefpirome for MRSA argues for further evaluation of this antibiotic for treatment of MRSA and other Gram-positive cocci, including enterococci.

Aminoglycosides↗
PubMed1989

Ciprofloxacin therapy for methicillin-resistant Staphylococcus aureus infections or colonizations.

Thirty patients were treated for colonization or for skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus. Three treatment regimens were evaluated, each progressively more aggressive. Our regimen was 750 mg of ciprofloxacin twice daily for 5 days, the second regimen was 750 mg of ciprofloxacin twice daily for 10 to 14 days, and the final regimen was 750 mg of ciprofloxacin twice daily plus 300 mg of rifampin twice daily for 21 days. It appears that ciprofloxacin alone produced an initial eradication rate in at least one site in 50% of the patients, regardless of whether the treatment was for 5 or up to 14 days. All of the patients with eradication became recolonized within 1 week posttherapy. When rifampin was combined with ciprofloxacin, the eradication rate was 100% when the isolates were susceptible to both agents, and these patients remained free of methicillin-resistant S. aureus at 1-week and 1-month follow-ups.

Ciprofloxacin↗
PubMed1989

D-lactic acid measurements in the diagnosis of bacterial infections.

Body fluids suspected of bacterial infection were cultured and examined for the presence of D-lactic acid, a specific bacterial metabolite. We examined 206 patients and 264 specimens. D-Lactic acid was found in concentrations of greater than or equal to 0.15 mM in 11 of 11 infected and 6 of 40 noninfected ascitic fluids, 6 of 6 infected and 4 of 33 noninfected pleural fluids, 4 of 4 infected and 0 of 13 noninfected synovial fluids, and 26 of 27 infected and 2 of 130 noninfected cerebrospinal fluids. The overall sensitivity was 79.7%, and the specificity was 99.5% when the D-lactic acid concentration was at least 0.15 mM. The most important clinical utility of the D-lactic acid measurement appears to be for patients with bacterial infection in various body compartments and in patients who have already received antimicrobial therapy. An elevation in D-lactic acid may indicate the presence of bacterial infection even when cultures are negative.

Ascitic Fluid↗
PubMed1989

Diagnosis of Mycobacterium bacteremia in patients with acquired immunodeficiency syndrome by direct examination of blood films.

Thirty acquired immunodeficiency syndrome patients with mycobacterial bacteremia documented by Du Pont Isolator (Du Pont Co., Wilmington, Del.) blood cultures underwent microscopic examination of buffy coat blood smears. Of 30 patients, 14 were culture positive for Mycobacterium avium-Mycobacterium intracellulare complex and 1 was positive for M. tuberculosis. Of 15 culture-positive patients, 13 had identifiable organisms on Kinyoun- or auramine-stained direct blood smears.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Effect of intravenous vancomycin on renal function.

In the past, vancomycin has been reported to cause renal failure during intravenous administration; however, more recently, such renal toxicity is alleged not to occur because of increased purity of the vancomycin preparations. In this study, 23 patients were prospectively examined during intravenous vancomycin administration for changes in renal function. Vancomycin was administered for an average of 15 days. The blood urea nitrogen (BUN) changes averaged +1.7 mg/dl and the creatinine changes averaged +0.06 mg/dl. Since the accuracy of the serum creatinine determination was +/- 0.3 mg/dl, clinically significant deterioration of renal function occurred in 4 patients or 17%. Even among these 4 patients with documented worsening of renal function, we suspect that deterioration was related to the infection being treated. With close monitoring of dosing, the propensity of vancomycin to cause nephrotoxicity may be less than once thought.

Adult↗
PubMed1989

Seizure propensity with imipenem.

Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.

Aged↗
PubMed1989

Brain lesions in patients with acquired immunodeficiency syndrome.

Infections involving the brain have become a major complication in patients with acquired immunodeficiency syndrome. We have reviewed 48 cases of central nervous system lesions in patients with acquired immunodeficiency syndrome. and its related complex. All patients had computed tomographic scans with contrast performed; 31 of 48 were intravenous drug abusers. Computed tomographic abnormalities found included 21 patients with multiple ring-enhancing lesions, 13 with single ring-enhancing lesions, 11 with single hypodense lesions, and three with multiple hypodense lesions. Twenty-five patients had a positive serologic reaction for Toxoplasma. Sixteen patients had brain tissues examined. Of the 16 patients, six had cerebral Toxoplasma (one with concomitant Mycobacterium tuberculosis), and ten had diagnoses other than toxoplasmosis (three of whom had a positive serologic reaction for Toxoplasma). Two patients had M tuberculosis; one patient had Nocardia asteroides with Salmonella enteritidis. Of the remaining seven patients, three had encephalitis of unknown cause, two had inconclusive tissue diagnoses, one had progressive multifocal leukoencephalopathy, and one had vasculitis. In the population of intravenous drug users, brain lesions from diseases other than toxoplasmosis may be just as prevalent. Attempts to obtain a diagnosis from brain tissue is highly recommended to permit the design of effective and specific therapy for those diseases amenable to therapy.

Acquired Immunodeficiency Syndrome↗