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Biomedical subjects

W E Sanders

Publications and source records attributed to W E Sanders.

At least 19 recordsLinked to original sources
PubMed2001

Potential impact of the VITEK 2 system and the Advanced Expert System on the clinical laboratory of a university-based hospital.

A study was designed to assess the impact of the VITEK 2 automated system and the Advanced Expert System (AES) on the clinical laboratory of a typical university-based hospital. A total of 259 consecutive, nonduplicate isolates of Enterobacteriaceae members, Pseudomonas aeruginosa, and Staphylococcus aureus were collected and tested by the VITEK 2 system for identification and antimicrobial susceptibility testing, and the results were analyzed by the AES. The results were also analyzed by a human expert and compared to the AES analyses. Among the 259 isolates included in this study, 245 (94.6%) were definitively identified by VITEK 2, requiring little input from laboratory staff. For 194 (74.9%) isolates, no inconsistencies between the identification of the strain and the antimicrobial susceptibility determined by VITEK 2 were detected by the AES. Thus, no input from laboratory staff was required for these strains. The AES suggested one or more corrections to results obtained with 65 strains to remove inconsistencies. The human expert thought that most of these corrections were appropriate and that some resulted from a failure of the VITEK 2 system to detect certain forms of resistance. Antimicrobial phenotypes assigned to the strains by the AES for beta-lactams, aminoglycosides, quinolones, macrolides, tetracyclines, and glycopeptides were similar to those assigned by the human expert for 95.7 to 100% of strains. These results indicate that the VITEK 2 system and AES can provide accurate information in tests for most of the clinical isolates examined and remove the need for human analysis of results for many. Certain problems were identified in the study that should be remediable with further work on the software supporting the AES.

Anti-Bacterial Agents↗
PubMed2000

Radiofrequency catheter ablation of supraventricular tachycardia substrates after mustard and senning operations for d-transposition of the great arteries.

OBJECTIVES: The purpose of this study was to determine the efficacy and risks of radiofrequency ablation of various forms of supraventricular tachycardia after Mustard and Senning operations for d-transposition of the great arteries. BACKGROUND: In this patient group, the reported success rate of catheter ablation of intraatrial reentry tachycardia is about 70% with a negligible complication rate. There are no reports of the use of radiofrequency ablation to treat other types of supraventricular tachycardia. METHODS: Standard diagnostic criteria were used to determine supraventricular tachycardia type. Appropriate sites for attempted ablation included 1) intraatrial reentry tachycardia: presence of concealed entrainment with a postpacing interval similar to tachycardia cycle length; 2) focal atrial tachycardia: a P-A interval < or =-20 ms; and 3) typical variety of atrioventricular (AV) node reentry tachycardia: combined electrographic and radiographic features. RESULTS: Nine Mustard and two Senning patients underwent 13 studies to successfully ablate all supraventricular tachycardia substrates in eight (73%) patients. Eight of eleven (73%) patients having intraatrial reentry tachycardia, 3/3 having typical AV node reentry tachycardia, and 2/2 having focal atrial reentry tachycardia were successfully ablated. Among five patients having intraatrial reentry tachycardia (IART) and not having ventriculoatrial (V-A) conduction, two suffered high-grade AV block when ablation of the systemic venous portion of the medial tricuspid valve/inferior vena cava isthmus was attempted. CONCLUSIONS: Radiofrequency catheter ablation can be effectively and safely performed for certain supraventricular tachycardia types in addition to intraatrial reentry. A novel catheter course is required for slow pathway modification. High-grade AV block is a potential risk of lesions placed in the systemic venous medial isthmus.

Adolescent↗
PubMed2000

A pilot study of antibiotic cycling in a hematology-oncology unit.

OBJECTIVE: To determine the safety and treatment efficacy of cycling antibiotic regimens for prophylaxis or treatment of patients with profound neutropenia. DESIGN: A prospective, nonrandomized, observational trial. SETTING: A 20-bed adult hematology-oncology inpatient unit at a university referral hospital. PATIENTS: Hospitalized adult patients with chemotherapy- or radiation-induced neutropenia (absolute neutrophil count less than 500 cells/mm3). INTERVENTION: Between July 1994 and January 1996, 295 hospitalized patients were evaluated on an intent-to-treat basis for the cycling protocol. Of these, 271 were eligible and assigned to one of four antibiotic regimens being used at the time of enrollment: (1) ceftazidime+vancomycin; (2) imipenem; (3) aztreonam+cefazolin; (4) ciprofloxacin+clindamycin. Data on infection rates and types, and antibiotic resistance patterns, toxicity, and effectiveness were collected. RESULTS: Twenty-four patients were excluded. Of the 271 evaluable patients, 123 (42%) were able to complete treatment on the assigned regimen. Of the 148 patients (50%) unable to do so, the reasons for failure included persistent fever (79%), breakthrough bacteremia (14%), and drug toxicity (7%). The antibiotic susceptibility profiles over the study period showed no increase in resistance. However, there was a marked increase in enterococcal infections. CONCLUSIONS: Our data show no significant increase in side effects or decrease in efficacy while cycling antibiotics among neutropenic patients and thus support further study of its role.

Adult↗
PubMed2000

Ability of the VITEK 2 advanced expert system To identify beta-lactam phenotypes in isolates of Enterobacteriaceae and Pseudomonas aeruginosa.

The Advanced Expert System (AES) was used in conjunction with the VITEK 2 automated antimicrobial susceptibility test system to ascertain the beta-lactam phenotypes of 196 isolates of the family Enterobacteriaceae and the species Pseudomonas aeruginosa. These isolates represented a panel of strains that had been collected from laboratories worldwide and whose beta-lactam phenotypes had been characterized by biochemical and molecular techniques. The antimicrobial susceptibility of each isolate was determined with the VITEK 2 instrument, and the results were analyzed with the AES to ascertain the beta-lactam phenotype. The results were then compared to the beta-lactam resistance mechanism determined by biochemical and molecular techniques. Overall, the AES was able to ascertain a beta-lactam phenotype for 183 of the 196 (93.4%) isolates tested. For 111 of these 183 (60.7%) isolates, the correct beta-lactam phenotype was identified definitively in a single choice by the AES, while for an additional 46 isolates (25.1%), the AES identified the correct beta-lactam phenotype provisionally within two or more choices. For the remaining 26 isolates (14.2%), the beta-lactam phenotype identified by the AES was incorrect. However, for a number of these isolates, the error was due to remediable problems. These results suggest that the AES is capable of accurate identification of the beta-lactam phenotypes of gram-negative isolates and that certain modifications can improve its performance even further.

Enterobacteriaceae↗
PubMed1998

Ischaemia of the index finger and thumb secondary to thrombosis of the radial artery in the anatomical snuffbox.

We report on nine patients who presented with spontaneous ischaemia of the index finger and thumb over an 11 year period. Arteriography revealed thrombosis of the radial artery in the region of the anatomical snuffbox with evidence of digital artery embolization in each. None had suffered direct trauma to the area or had a demonstrable proximal source for thrombus. While the cause of radial artery thrombosis in our patients in not entirely clear, local inflammation and/or systemic disease may predispose to this entity.

Adult↗
PubMed1998

Cefepime-aztreonam: a unique double beta-lactam combination for Pseudomonas aeruginosa.

An in vitro pharmacokinetic model was used to determine if aztreonam could enhance the pharmacodynamics of cefepime or ceftazidime against an isogenic panel of Pseudomonas aeruginosa 164, including wild-type (WT), partially derepressed (PD), and fully derepressed (FD) phenotypes. Logarithmic-phase cultures were exposed to peak concentrations achieved in serum with 1- or 2-g intravenous doses, elimination pharmacokinetics were simulated, and viable bacterial counts were measured over three 8-h dosing intervals. In studies with cefepime and cefepime-aztreonam against the PD strain, samples were also filter sterilized, assayed for active cefepime, and assayed for nitrocefin hydrolysis activity before and after overnight dialysis. Against WT strains, the cefepime-aztreonam combination was the most active regimen, but viable counts at 24 h were only 1 log below those in cefepime-treated cultures. Against PD and FD strains, the antibacterial activity of cefepime-aztreonam was significantly enhanced over that of each drug alone, with 3.5 logs of killing by 24 h. Hydrolysis and bioassay studies demonstrated that aztreonam was inhibiting the extracellular cephalosporinase that had accumulated and was thus protecting cefepime in the extracellular environment. In contrast to cefepime-aztreonam, the pharmacodynamics of ceftazidime-aztreonam were not enhanced over those of aztreonam alone. Further pharmacodynamic studies with five other P. aeruginosa strains producing increased levels of cephalosporinase demonstrated that the enhanced pharmacodynamics of cefepime-aztreonam were not unique to the isogenic panel. The results of these studies demonstrate that aztreonam can enhance the antibacterial activity of cefepime against derepressed mutants of P. aeruginosa producing increased levels of cephalosporinase. This positive interaction appears to be due in part to the ability of aztreonam to protect cefepime from extracellular cephalosporinase inactivation. Clinical evaluation of this combination is warranted.

Aztreonam↗
PubMed1997

Antimicrobial resistance with focus on beta-lactam resistance in gram-negative bacilli.

beta-Lactam antibiotics are the most frequently prescribed antibiotics worldwide. Therefore, it is not surprising that resistance to this very important class of agents poses an increasingly complex and perplexing problem for physicians. Among the variety of mechanisms that can provide resistance to beta-lactam antibiotics in gram-negative bacilli, the production of beta-lactamase is by far the single most important factor. With the introduction of newer beta-lactam agents observed changes in beta-lactamases include the increased prevalence of older enzymes, the appearance of new enzymes, and alteration in the level of expression of the enzymes. These changes have been responsible for resistance to newer cephalosporins, monobactams, carbapenems, and beta-lactamase inhibitor/beta-lactam drug combinations. Resistance to beta-lactam antibiotics has also emerged through alterations in the targets of the drugs, the penicillin-binding proteins, and through alterations in outer membrane permeability of the organisms to the drugs. With some beta-lactam agents, multiple mechanisms must be acquired before clinically relevant levels of resistance are attained. This is especially true for carbapenems and fourth generation cephalosporins. Nevertheless, resistance to beta-lactam antibiotics is on the rise among clinical isolates of gram-negative bacilli, and only through more judicious use of these agents can their usefulness for treatment and prevention of infections be preserved.

Anti-Bacterial Agents↗
PubMed1997

Flexor carpi radialis approach for carpal tunnel release.

A technique for dividing the transverse carpal ligament has been developed in order to decrease the incidence of pillar pain. The carpal ligament splits around the flexor carpi radialis (FCR) tendon into two leaves as it approaches its radial attachments. The new approach uses the FCR as a guide to divide these attachments under direct visualization, thereby releasing the carpal tunnel. This technique has been used on 87 hands, with 79 (91%) obtaining complete or partial relief of preoperative symptoms. Pillar tenderness resolved quickly and there were few complications. The FCR approach to carpal tunnel release couples the advantages of direct visualization of the carpal canal contents with the decreased disruption of palmar skin and soft tissues, thereby reducing pillar pain without increasing the risk of surgical complications.

Adult↗
PubMed1997

Penicillin-binding proteins and induction of AmpC beta-lactamase.

In competition assays for radiolabeled penicillin, penicillin-binding proteins (PBPs) 4, 7a, and 7b showed very high affinities for strong inducers of AmpC beta-lactamase. Loss of PBP 4 resulted in diminished inducibility. This suggests that if PBPs are involved in induction of AmpC beta-lactamase, there is probably a redundancy in function among the different PBPs.

Bacterial Proteins↗
PubMed1997

Enterobacter spp.: pathogens poised to flourish at the turn of the century.

Knowledge of the genus Enterobacter and its role in human disease has expanded exponentially in recent years. The incidence of infection in the hospital and the community has increased. New clinical syndromes have been recognized. Enterobacter spp. have also been implicated as causes of other syndromes that traditionally have been associated almost exclusively with more easily treatable pathogens, such as group A streptococci and staphylococci. Rapid emergence of multiple-drug resistance has been documented in individual patients during therapy and in populations and environments with strong selective pressure from antimicrobial agents, especially the cephalosporins. Therapeutic options for patients infected with multiply resistant strains have become severely limited. Carbapenems or, alternatively, fluoroquinolones are the most predictively active options, although resistance to both classes has been observed on rare occasions. Enterobacter spp. appear well adapted for survival and even proliferation as the turn of the century approaches.

Anti-Bacterial Agents↗
PubMed1996

Piperacillin/tazobactam: a critical review of the evolving clinical literature.

Piperacillin/tazobactam is the most recently approved combination of a beta-lactam agent with an inhibitor of bacterial beta-lactamases. It has a broader spectrum than do preceding inhibitor-drug combinations, and it is generally more potent. In terms of clinical and microbiological outcomes, comparative studies have shown that piperacillin/tazobactam was comparable to imipenem (1.0 g q8h) and to clindamycin plus gentamicin for intraabdominal infections, to clindamycin plus gentamicin for infections of the skin and skin structures and pelvic tissues in women, and to ticarcillin/clavulanate for skin and soft-tissue infections. Piperacillin/tazobactam was statistically superior to imipenem (0.5 g q8h) for intraabdominal infections, to ticarcillin/clavulanate for community-acquired lower respiratory tract infections, and to ceftazidime for nosocomial lower respiratory tract infections and febrile episodes in neutropenic patients. Adverse effects with piperacillin/tazobactam were generally of only mild-to-moderate severity. Piperacillin/tazobactam may be especially useful for the treatment of infections that are likely to be polymicrobial or to be due to any one of an array of aerobic or anaerobic bacteria; this agent may also be useful in situations where organisms with plasmid-mediated beta-lactamases have become problematic.

Drug Therapy, Combination↗
PubMed1996

Efficacy of cefepime in the treatment of infections due to multiply resistant Enterobacter species.

Cefepime is a new cephalosporin with an enhanced antibacterial potency and spectrum. More rapid penetration into many gram-negative bacilli, targeting of multiple penicillin-binding proteins, and resistance to inactivation by many beta-lactamases account for its activity against organisms that have developed resistance to agents such as ceftazidime, cefotaxime, or ceftriaxone. This study identified 16 patients with 17 infections due to Enterobacter species organisms with reduced susceptibility or resistance to ceftazidime. Most isolates were multiply resistant to other beta-lactam drugs as well, but all were susceptible to cefepime. All 17 infections, which included pneumonia, urinary tract infection, intraabdominal infection, and bacteremia, responded clinically to intravenous cefepime. In particular, cefepime was successfully used in the management of cases of chronic infection that had responded poorly to repeated therapy with imipenem, aminoglycosides, or ciprofloxacin. Eradication of Enterobacter species organisms occurred at 15 (88.2%) of the 17 sites of infection. No emergence of resistance to cefepime was noted.

Cefepime↗
PubMed1996

Ventricular fibrillation induction using nonsynchronized low energy external shock during rapid ventricular pacing: method of induction when fibrillation mode of ICD fails.

Third-generation implantable cardioverter defibrillators (ICD) are frequently implanted with nonthoracotomy systems and provide noninvasive methods for electrical stimulation and ventricular fibrillation induction. These modalities facilitate postoperative testing of the ICD. Rapid right ventricular burst pacing via the defibrillator is commonly used for initiation of ventricular tachyarrhythmias. However, with the available third-generation devices, ventricular fibrillation (VF) induction may be impossible in up to 19% of the patients. In these cases, transvenous placement of a right ventricular catheter has been required to generate VF and appropriately evaluate the device. We report a new technique of noninvasive induction of VF using a low energy external nonsynchronized shock delivered during ICD fibrillation induction pacing. In three patients, after all efforts to induce VF by the Ventritex Cadence V-100 had failed, a 20 J nonsynchronized shock was delivered during rapid RV pacing. This resulted in VF on the first attempt in all patients. This noninvasive technique of VF initiation may provide a useful clinical approach to ICD testing that eliminates the costs and risks of an invasive procedure.

Adult↗
PubMed1995

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis.

The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at > or = 8.0 micrograms/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 micrograms/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4- to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.

Antitubercular Agents↗
PubMed1995

Thrombotic thrombocytopenia induced in dogs and pigs. The role of plasma and platelet vWF in animal models of thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenia with severe depletion of plasma von Willebrand factor (vWF) was induced in normal large animals (5 dogs and 2 pigs) by botrocetin, a Bothrops factor requiring vWF for platelet agglutination. Botrocetin (90 to 100 U/kg, 2.14 to 2.38 mg/kg, in a single i.v. injection) reduced plasma vWF activity to < 0.1 U/mL for 24 hours. During this period, multimeric analysis of plasma vWF antigen (Ag) revealed the loss of intermediate- and high-molecular-weight forms with a concomitant increase in lower molecular weight forms. A moderate reduction in factor VIII (FVIII) activity was observed. The vWF reduction was accompanied by transient thrombocytopenia and prolonged bleeding times during the deficiency state. Occlusive platelet thrombi were detected by transmission electron microscopy in the microcirculation of lung and spleen but not kidney or brain 30 minutes after the botrocetin injection. Recovery of plasma vWF and platelet count occurred within 48 hours and was associated with the appearance in the plasma of unusually large forms of vWF:Ag multimers. The vWF:Ag multimer distribution was normal at 72 hours. The ultrastructural distribution of vWF in unstimulated normal porcine and canine platelets was examined by using immunogold staining. VWF was detected in the alpha-granules of normal pig platelets but was not observed in platelets from normal dogs. However, both animals developed thrombotic thrombocytopenia when injected with botrocetin. A second group of animals (2 dogs and 3 pigs) with von Willebrand disease (vWD) was given a single botrocetin injection (90 to 100 U/kg). No thrombocytopenia occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗