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Biomedical subjects

W E Sanders

Publications and source records attributed to W E Sanders.

At least 37 records · Page 2Linked to original sources
PubMed1995

Fluoroquinolone resistance in staphylococci: new challenges.

Staphylococci show only marginal susceptibility to the newer fluoroquinolones. Minimum inhibitory concentrations (MICs) for susceptible strains usually range from 0.25 to 2.0 mg/l. As a single mutational event involving the gyrase target or permeability diminishes fluoroquinolone susceptibility fourfold on average, such a mutation in staphylococci would lead to a clinical level of resistance. Therefore, it is not surprising that in some institutions, the use of fluoroquinolones has been quickly followed by greatly increased prevalence of fluoroquinolone-resistant staphylococci. The greatest increase in resistance has been seen among methicillin-resistant staphylococci although increased prevalence of resistance among Staphylococcus saprophyticus and other methicillin-susceptible staphylococci has also been reported. Clinical isolates of staphylococci recovered since the introduction of the fluoroquinolones fall into three fluoroquinolone susceptibility groups: susceptible (MIC < 0.5 mg/l), moderately resistant (MIC 0.5 to 4 mg/l) and highly resistant (MIC > 4 mg/l). The first group represents wild type strains while the second and third groups represent single- and multiple-step mutants, respectively. To prevent increasing prevalence of isolates in the second and third groups, it would be prudent to avoid use of quinolones whenever possible. However, when it is necessary, a fluoroquinolone, which achieves serum/tissue levels eight times the MIC of the infecting strain, should be used.

Anti-Infective Agents↗
PubMed1994

Catheter ablation of sinoatrial node reentrant tachycardia.

OBJECTIVES: This study evaluates 1) the safety and efficacy of catheter delivery of radiofrequency current to eliminate sustained sinoatrial node reentrant tachycardia; 2) the incidence of sinoatrial node reentrant tachycardia in the current group of patients undergoing electrophysiologic study for paroxysmal supraventricular tachycardia; and 3) the association of sinoatrial node reentrant tachycardia with other tachyarrhythmias. BACKGROUND: Sustained sinoatrial node reentrant tachycardia is an uncommon cause of paroxysmal supraventricular tachycardia that is reported to occur infrequently in conjunction with other arrhythmias. Although pharmacologic and surgical therapies are available, there is limited information with regard to catheter ablation of sinoatrial node reentrant tachycardia. METHODS: Ten patients with sustained sinoatrial node reentrant tachycardia underwent electrophysiologic study and radiofrequency current ablation. Patients were followed up for 9.2 +/- 6.0 months. RESULTS: Of 343 consecutive patients referred for electrophysiologic evaluation of paroxysmal supraventricular tachycardia, 11 (3.2%) were found to have inducible sustained sinoatrial node reentrant tachycardia. Nine of the 11 patients had other associated arrhythmias, including atrioventricular (AV) node reentrant tachycardia (6 patients), AV reciprocating tachycardia (2 patients), ectopic atrial tachycardia (2 patients) and bundle branch reentrant tachycardia (1 patient). In 10 patients, direct ablation of sinoatrial node reentrant tachycardia was attempted and was successful in all (confidence interval for failure 0-0.26). Sinoatrial node reentrant tachycardia was eliminated with a median of four radiofrequency current applications (range 1 to 10) at 20 to 30 W. Successful ablation site characteristics during sinoatrial node reentrant tachycardia included 1) atrial activation > or = 35 ms (mean 44 +/- 8 ms) before the onset of the surface P wave, 2) atrial activation > or = 20 ms (mean 28 +/- 6 ms) before the onset of high right atrial activation, and 3) significantly prolonged and fractionated electrograms (mean duration 87 +/- 21 ms). No complications were encountered, and there have been no recurrences of sinoatrial node reentrant tachycardia. CONCLUSIONS: Sinoatrial node reentrant tachycardia may be effectively and safely treated with radiofrequency current ablation at the site of earliest atrial activation.

Adult↗
PubMed1994

Effects of different test conditions on the susceptibility of Mycobacterium fortuitum and Mycobacterium chelonae to amikacin.

Eighteen rapidly growing mycobacteria were tested for susceptibility to amikacin by six different antibiotic susceptibility procedures to assess method variability and factor variation within a single method. Using amikacin MICs determined by the microdilution method as the reference standard, results for Mycobacterium chelonae were on average eight-fold higher by the macrodilution method and two-fold higher by the BACTEC, 1% standard proportion, and agar dilution methods. For Mycobacterium fortuitum, macrodilution MICs were on average four-fold higher than microdilution results; however, for this species, agar dilution, the 1% standard proportion method, and the BACTEC method showed good correlation with microdilution testing. The use of different test media and incubation in increased CO2 tension increased amikacin MICs for Mycobacterium chelonae. An inoculum effect was observed with both species, especially when the organism concentration increased from 10(5) cfu/mL to 10(6) cfu/mL for broth testing and 10(5) to 10(6) cfu per spot for agar dilution. These results indicate that different antibiotic susceptibility methods and test conditions markedly influence MICs of amikacin for these rapidly growing mycobacteria.

Amikacin↗
PubMed1994

USA resistance patterns among UTI pathogens.

The fluoroquinolones are a new, potent class of antimicrobials which are heavily prescribed in the United States. Resistance to these agents has developed primarily in organisms that are inherently less sensitive, such as Staphylococcus spp. and Pseudomonas spp., but also, in some centres, in more sensitive organisms, such as members of the Enterobacteriaceae. Because the fluoroquinolones are a valuable class of broad-spectrum antibiotics, it is desirable that their usefulness be conserved by adopting measures to prevent or minimize the development of resistance. One obvious approach to this is to restrict their use, preventing overuse or misuse. The therapy of urinary tract infections is a major area in which fluoroquinolone usage could be reduced or rationalized. Although these agents are highly efficacious in the therapy of urinary tract infections, so too are older, less expensive agents such as nitrofurantoin, co-trimoxazole, sulphonamides and amoxycillin. From considerations of both economy and minimizing the development of resistance there appears to be little justification for using fluoroquinolones routinely to treat urinary tract infections, except where other oral agents may not be well tolerated or are unlikely to be effective.

Anti-Infective Agents↗
PubMed1993

Decimal assay for additivity of drugs permits delineation of synergy and antagonism.

Although there are many in vitro tests for drug interactions, few possess a linear, predictable dose-dependent end point or have a precise definition for additivity. Therefore, a new test with both of these features, the decimal assay for additivity, was developed. This test is based on a disk diffusion assay and the strict linear relationship between drug mass and size of the inhibition zone. When the decimal assay for additivity was applied to combinations known on a mechanistic basis to be additive, synergistic, or antagonistic, results of the new test always reflected the expected drug interaction. For example, synergy between trimethoprim and sulfamethoxazole was detected in tests with Escherichia coli and Haemophilus influenzae, as was antagonism between cefoxitin and cefotaxime in tests with Enterobacter cloacae. Quinolones plus chloramphenicol appeared to be antagonistic. In addition to correctly identifying the drug interaction, the decimal assay for additivity identified the drug ratio producing the maximal drug interaction. These results suggest that the decimal assay for additivity should prove very useful in future studies of drug interactions.

4-Quinolones↗
PubMed1992

Molecular cloning and analysis of in vivo expression of murine P-selectin.

P-selectin (CD62) is a rapidly inducible cell surface adhesion molecule that is expressed on platelets and endothelial cells and mediates their interaction with leukocytes. In vitro studies have suggested that this receptor may play an important role in hemostasis and in inflammatory response to tissue injury. We report the molecular cloning and sequencing of murine cDNA for P-selectin. The lectin, epidermal growth factor (EGF)-like, transmembrane, and cytoplasmic domains are highly conserved between mouse and human, with an overall amino acid identity of 79%. To further investigate the biology of this adhesion molecule in vivo, we analyzed mRNA levels for P-selectin in mice after injection with endotoxin. Northern blot data indicate that the cellular response in vivo includes a rapid increase in the level of mRNA, presumably for new synthesis of P-selectin. The increase in mRNA is maximal at 4 hours, and turnover is relatively rapid, with levels of RNA having decreased substantially by 6 hours following stimulation with endotoxin. After administration of endotoxin, the highest levels of mRNA expression were detected in liver, lung, kidney, and heart.

3T3 Cells↗
PubMed1992

Does cocaine cause coronary vasospasm in chronic cocaine abusers? A study of coronary and systemic hemodynamics.

The pathogenesis of acute myocardial ischemia or infarction following cocaine abuse is not known. Cocaine causes an increase in circulating catecholamines. Therefore alpha-adrenergic mediated focal or generalized coronary artery spasm has been presumed to be the likely mechanism to induce ischemia. However, coronary vasospasm in chronic cocaine abusers has not been demonstrated angiographically. Moreover, it has been observed that patients commonly manifest ischemic changes hours up to a week after abusing cocaine. In order to evaluate direct effects of cocaine on coronary vasculature, 6 chronic cocaine abusers admitted with prolonged chest pain and electrocardiographic ST- and T-wave changes were studied. Cocaine administered intravenously (maximum 32 mg) produced subjective sensation of central nervous stimulation (the "high") in all patients. However there was no significant change in coronary artery diameter (assessed by computer-assisted quantitative technique), myocardial perfusion (assessed by contrast echocardiography) or left ventricular wall motion (assessed by two-dimensional echocardiography) as compared with the baseline values. Coronary sinus flow (thermodilution) showed an upward trend, a probable reflection of a significant increase in cardiac output (average 62%, p less than 0.007). Despite a significant elevation in heart rate (average 56%, p less than 0.007), mean systemic arterial pressure (average 12%, p less than 0.05) and rate-pressure product (average 69%, p less than 0.005), no symptomatic or acute electrocardiographic changes were observed. It is concluded that recreational doses of cocaine do not cause focal or generalized coronary vasospasm or reduced myocardial perfusion in patients who present with chest pain temporally related to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

beta-Lactam resistance in gram-negative bacteria: global trends and clinical impact.

Microbial drug resistance is an inescapable consequence of the utilization of antimicrobial agents in a given environment. Nowhere is the importance of resistance more evident than among agents of the beta-lactam family. Trends toward increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae, where ampicillin resistance varies from 1% to 64% globally. For Escherichia coli, ampicillin resistance has risen to > or = 50% in high-risk populations, and resistance to third-generation cephalosporins is now being seen in certain areas. Inducible beta-lactamases have been responsible for increasing multiple beta-lactam resistance among certain Enterobacteriaceae and Pseudomonas aeruginosa, and this has been associated with increased use of newer cephalosporins. Xanthomonas maltophilia with its two inducible beta-lactamases is becoming an increasingly important nosocomial pathogen, especially in areas of heavy imipenem utilization. Only through the recognition of factors associated with increasing resistance and the mechanisms responsible can strategies be designed for minimizing beta-lactam resistance.

Ampicillin Resistance↗
PubMed1992

Oral ofloxacin: a critical review of the new drug application.

Ofloxacin is a fluoroquinolone with activity against gram-positive and gram-negative aerobic and facultatively anaerobic bacteria, chlamydiae, and some related organisms, such as mycoplasmas or mycobacteria. It has been administered orally to 3,903 patients described in the New Drug Application (NDA) submitted to the U.S. Food and Drug Administration. Although some components of the NDA lack scientific rigor or fail to mimic clinical practice, other components and the collective whole identify important potential advantages and limitations of the new drug. Ofloxacin was effective in the treatment of infections of the skin, soft tissues, urinary tract, and lower respiratory tract as well as in that of gonococcal and nongonococcal urethritis and prostatitis due to sensitive organisms. Adverse reactions were relatively infrequent, generally mild, and usually self-limiting. Symptoms involving the gastrointestinal tract and the central nervous system predominated. The emergence of resistance and superinfections were uncommon. Few adverse drug interactions were encountered, although antacids may diminish gastrointestinal absorption. In certain defined clinical situations, ofloxacin appears to be a useful addition to the therapeutic armamentarium.

Administration, Oral↗
PubMed1992

Long term epidemiological analysis of Citrobacter diversus in a neonatal intensive care unit.

A prolonged outbreak of Citrobacter diversus central nervous system infection among hospitalized term infants, peaking in 1979, ceased with establishment of nurse-patient cohorting. The outbreak was attributed to dissemination of an epidemic strain among infants in an antiquated neonatal intensive care unit. When C. diversus colonization recurred within the new neonatal intensive care unit in 1984, cohorting and bacteriologic surveillance were reinstituted. By utilizing biotypes, plasmid profiles and antibiograms, four different C. diversus strains were identified circulating during 1979. Strains recovered between 1984 and 1988 from neonatal intensive care unit infants were similar to those from community-acquired sources. A strain considered avirulent in 1979 was found causing bacteremia in two infants (one with central nervous system disease) in 1984 to 1988. During cohorting C. diversus acquisition was 0.019/patient-month; after cohorting ceased it was 0.017/patient-month. Multiple source introductions appeared to occur with different C. diversus strains, some causing infant disease. No efficacy of cohorting was evident.

Citrobacter↗
PubMed1992

Lack of evidence of efficacy of cohorting nursing personnel in a neonatal intensive care unit to prevent contact spread of bacteria: an experimental study.

Nurse cohorting was investigated in a modern neonatal intensive care unit (NICU). During 99 days bacterial infection and colonization rates were determined in 100 infants experimentally assigned cohort or noncohorted care. Colonizing isolate identity was determined by plasmid profile analyses and biotyping in weekly surveillance cultures. Between Days 2 and 7, 3 infections occurred in cohorted infants but none in noncohorted ones. No secondary spread of infection or definitive colonization cluster occurred. The first colonization rate, at any site, was 0.53/patient-week in the noncohorted and 0.3 to 0.4 in the cohorted units (P greater than 0.05). Colonization ratios with species other than usual skin bacteria in the respiratory tract and with species other than Escherichia coli in the rectum were lower for noncohorted infants. Effective infection control practices in a modern NICU, including alcohol hand antisepsis, should obviate a need for cohorting.

Bacterial Infections↗
PubMed1992

Advantages of "epitenon first" suture placement technique in flexor tendon repair.

A carefully performed flexor tendon repair should not result in enlargement of the tenorrhaphy. However, many current repair techniques using a core suture followed by an epitendinous suture have this drawback. A technique of placing the epitenon suture first, followed by the core suture, is discussed, and the advantages of the technique are emphasized.

Humans↗
PubMed1991

Contrast opacification of left ventricular myocardium following intravenous administration of sonicated albumin microspheres.

Albunex is a new echocardiographic (2-D echo) contrast agent that traverses the pulmonary vasculature when injected intravenously in humans. We examined whether intravenous Albunex resulted in changes in myocardial intensity of sufficient magnitude to produce time intensity curves (TICs). Thirty mildly hypertensive patients were divided into three groups of 10. Each patient received three injections of intravenous Albunex (group I dosages: 0.01, 0.02, and 0.04 cm3/kg; group II: 0.04, 0.06, and 0.08 cm3/kg; group III: 0.08, 0.1, and 0.12 cm3/kg) and two control injections of 5% human serum albumin while imaging with 2-D echo (phased-array; apical four-chamber). Fourty-three injections showed complete opacification of the left ventricle. Videointensity analysis of digitized end-diastolic frames produced myocardial TICs (total as well as background-subtracted intensity curves) in 20 of 43 injections. By visual inspection, a myocardial contrast effect was seen in 10 of 43 injections. Detection of myocardial TICs was dose-related (0 of 7 in group I, 9 of 18 in group II, 11 of 18 in group III) and always paralleled the degree of left ventricular opacification. No myocardial contrast effect was observed in any patient during control injections of albumin or in any patient in whom the injection of Albunex did not result in left ventricular opacification. Thus myocardial opacification with intravenous Albunex can be detected simultaneously with good left ventricular opacification. The potential significance of the myocardial opacification observed is discussed.

Adolescent↗
PubMed1991

Oral ofloxacin for the treatment of acute bacterial pneumonia: use of a nontraditional protocol to compare experimental therapy with "usual care" in a multicenter clinical trial.

PURPOSE: This multicenter study was designed to compare an exclusively oral regimen with "usual care" in patients hospitalized with acute bacterial pneumonia. PATIENTS AND METHODS: One hundred forty-seven patients were enrolled. All patients presented with a clinical picture consistent with pneumonia: (1) clinical symptoms of a lower respiratory tract infection, such as chest pain, cough, and production of purulent sputum; (2) roentgenographic infiltrate compatible with acute infection; and (3) Gram's stain of purulent sputum or other appropriate bronchopulmonary specimen containing gram-negative organisms, staphylococci, or pneumococci. All patients required hospitalization. The design was a parallel-group, open-label study with randomization in blocks of four. Ofloxacin, a new fluoroquinolone antimicrobial agent, was administered orally or by nasogastric tube, 400 mg every 12 hours. This was compared with the individual investigator's best selection of therapy that was administered parenterally, at least initially. RESULTS: One hundred thirty-three patients were evaluable after exclusions for deviation from protocol, early death due to unrelated causes, incorrect diagnosis, or early adverse drug reactions. All 69 patients treated with ofloxacin and 61 of 64 control patients had favorable clinical and microbiologic responses. There were no statistically significant differences between the groups in terms of demographics, therapeutic outcome, and duration of therapy. There were few side effects overall and rates were similar for the two groups. CONCLUSIONS: An exclusively oral regimen, in this case ofloxacin, may be substituted for parenteral therapy in selected patients with pneumonia. This might significantly reduce costs and risks to the patient.

Administration, Oral↗
PubMed1991

Ceftriaxone in treatment of serious infections. Urinary tract infections.

Ceftriaxone is active against many gram-negative bacillary uropathogens. It achieves very high levels in urine and proximate tissue following single daily doses. Clinical and bacteriologic results in infections due to susceptible organisms have been excellent. Additional comparative studies with longer follow-up may assist in further delineating the relative role of ceftriaxone in management of infections of the urinary tract.

Bacterial Infections↗
PubMed1991

In vitro studies with Bay V 3522, a new oral cephalosporin.

The in vitro activities of Bay v 3522, cefaclor, cephalexin, cefuroxime, cefixime, amoxicillin/clavulanate (2:1) and reference penicillins were compared against 314 clinical isolates of Gram-positive and Gram-negative bacteria and nine strains of Escherichia coli that differed in their outer membrane proteins in agar dilution tests with an inoculum of 10(4) cfu/spot. The beta-lactamase stabilities of the cephalosporins were also evaluated by spectrophotometric assay using 21 different beta-lactamases. Bay v 3522 was the most potent cephalosporin overall against Gram-positive pathogens, but slightly less active than amoxicillin/clavulanate. In addition to being highly active against streptococci (MIC90 = 0.25 micrograms/ml) and methicillin-susceptible staphylococci (MIC90 = 1.0 micrograms/ml), Bay v 3522 was markedly more active than the other cephalosporins against Enterococcus faecalis (MIC90 = 4 micrograms/ml). Bay v 3522 was less potent against Gram-negative pathogens, especially nosocomial isolates of Escherichia coli and Klebsiella pneumoniae (MIC90 greater than 64 micrograms/ml), but was active against Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and beta-lactamase-negative Neisseria gonorrhoeae (MIC90 = 1.0 micrograms/ml0. Hydrolysis of Bay v 3522 by most beta-lactamases examined was significantly less than that observed for cephalothin and cefaclor; similar to that observed with cephalexin; and less than that observed with cefixime and cefuroxime. None of the beta-lactamases examined hydrolysed Bay v 3522 at a rate greater than 20 nmol/min/mg. The in vitro potency of Bay v 3522 against Gram-positive and fastidious Gram-negative pathogens and its resistance to hydrolysis by beta-lactamases produced by them support further investigation of this cephalosporin as a new oral therapeutic agent.

Anti-Bacterial Agents↗