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Biomedical subjects

D N Fish

Publications and source records attributed to D N Fish.

At least 19 recordsLinked to original sources
PubMed2004

Surveillance of multi-drug resistant Pseudomonas aeruginosa in an urban tertiary-care teaching hospital.

Antimicrobial resistance in Pseudomonas aeruginosa is a serious clinical problem. To determine the incidence of multi-drug resistant P. aeruginosa, resistance rates of P. aeruginosa clinical isolates against commonly used antibiotics were evaluated for the period 1998 to 2002. Multi-drug resistance was defined as resistance to at least three of the four drugs, ceftazidime, imipenem, ciprofloxacin, and tobramycin. Resistance to most anti-pseudomonal agents has increased by >20% over the five-year period, with dramatic increases observed with fluoroquinolones, tobramycin, and imipenem (resistance increased by 34-37%). In 1998, 78% of isolates were susceptible to all four anti-pseudomonal agents and no isolate was considered multi-drug resistant. However, in 2002, only 27% of isolates were sensitive to all four of the drugs and 32% were considered multi-drug resistant. Multi-drug resistance in individual institutions may be significantly higher than rates reported in nationwide surveillance studies and may more accurately reflect the true magnitude of local resistance problems. On-going surveillance within individual institutions is critical for the selection of appropriate empiric antimicrobial therapy.

Anti-Bacterial Agents↗
PubMed2001

Valacyclovir inhibition of recovery of ocular herpes simplex virus type 1 after experimental reactivation by laser in situ keratomileusis.

PURPOSE: To determine whether the systemic administration of valacyclovir (Valtrex) reduces ocular shedding of herpes simplex virus type 1 (HSV-1) after laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit latency model. SETTING: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. METHODS: New Zealand White rabbits latently infected with HSV-1 W strain were divided into 3 groups. The first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of valacyclovir; and the third (control), saline. One half the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with 1 dose before LASIK. The HSV-1 ocular shedding was determined from eye cultures for 7 days after LASIK. RESULTS: The administration of both 100 mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of eyes (1/16 in both groups) and the total number of HSV-1 shedding days (1/122 and 2/122, respectively) from which HSV-1 was recovered compared to the control group (7/16 [P =.0396] and 14/129 [P <.007], respectively). CONCLUSIONS: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding after LASIK in the NZW rabbit latency model. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode while on valacyclovir antiviral prophylaxis.

Acyclovir↗
PubMed2001

Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients.

The pharmacokinetics of intravenously administered levofloxacin and ciprofloxacin were studied in intensive care unit patients during continuous venovenous hemofiltration (CVVH; four patients received levofloxacin, and five received ciprofloxacin) or hemodiafiltration (CVVHDF; six patients received levofloxacin, and five received ciprofloxacin). Levofloxacin clearance was substantially increased during both CVVH and CVVHDF, while ciprofloxacin clearance was affected less. The results of this study suggest that doses of levofloxacin of 250 mg/day and ciprofloxacin of 400 mg/day are sufficient to maintain effective drug concentrations in the plasma of patients undergoing CVVH or CVVHDF.

Adult↗
PubMed2001

Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients.

The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 +/- 13.0 years [standard deviation]; mean weight, 96.7 +/- 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t(1/2)) of cefepime were 35.9 +/- 6.0 ml/min and 12.9 +/- 2.6 h during CVVH versus 46.8 +/- 12.4 ml/min and 8.6 +/- 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CL(S), respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CL(S) of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC <or= 8 microg/ml) during CVVH or CVVHDF.

Adult↗
PubMed2001

Use of enteral nutrition for stress ulcer prophylaxis.

OBJECTIVE: To review the controversies involving the use of enteral nutrition support for stress ulcer prophylaxis and formulate recommendations. DATA SOURCES: A MEDLINE search (1966-December 2000) was conducted using the MeSH of nutrition, ulcer, critical care, and acid to identify relevant articles. References of selected articles were reviewed, and relevant abstracts from critical care or gastrointestinal journals identified. DATA EXTRACTION: Animal and human data from prospective studies, retrospective studies, and case series were evaluated for the effects of enteral nutrition on gastric pH, intramucosal pH, gastrointestinal blood flow, development of macroscopic mucosal erosions, and hemorrhage. DATA SYNTHESIS: Intragastric administration of enteral nutrition has variable effects on gastric pH, enhances regional distribution of gastrointestinal blood flow, and may lower intramucosal pH. All substrates (carbohydrate, lipid, amino acid), when administered into the stomach, reduce the occurrence of mucosal erosions but do not entirely prevent their development. Few studies of stress ulcer prophylaxis regimens have reported use of enteral nutrition. Limited retrospective data suggest enteral nutrition support may be effective for preventing gastrointestinal hemorrhage, but the results of prospective studies are confounded by poor study design. CONCLUSIONS: Definitive recommendations regarding the role of enteral nutrition for stress ulcer prophylaxis are not possible due to the lack of prospective, randomized studies. Therefore, the use of enteral nutrition as the only therapeutic agent for stress ulcer prophylaxis should be discouraged until definitive data are available. Initiation and discontinuation of pharmacologic stress ulcer prophylaxis should be independent of enteral nutrition.

Animals↗
PubMed2001

Gatifloxacin, an advanced 8-methoxy fluoroquinolone.

Gatifloxacin is a new 8-methoxy-fluoroquinolone antibiotic approved for use in the United States in December 1999. It has a broad spectrum of activity with potent activity against gram-positive bacteria, including penicillin-resistant Streptococcus pneumoniae, as well as excellent activity against gram-negative and atypical organisms. Gatifloxacin is available in both oral and injectable forms and is administered once/day. Bioavailability is 96%, with a plasma half-life of approximately 8 hours in individuals with normal renal function. Elimination is primarily renal excretion of unchanged drug with no cytochrome P450-mediated metabolism. The drug is distributed extensively into tissues and fluids and has a favorable pharmacodynamic profile against important pathogens. It had excellent efficacy in clinical studies of acute sinusitis, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, complicated and uncomplicated urinary tract infections and pyelonephritis, skin and skin structure infections, and uncomplicated gonococcal infections. The agent is well tolerated, with no evidence of hepatic, cardiac, or phototoxicity noted thus far. Drug interactions are uncommon; however, like other fluoroquinolones, coadministration with multivalent cations should be avoided due to significantly decreased absorption. Gatifloxacin should prove to be a safe and effective agent for a wide variety of infections.

Animals↗
PubMed2001

Fluoroquinolone adverse effects and drug interactions.

Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug-drug interaction profiles. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Beginning with the development of fluoroquinolones, such as norfloxacin and ciprofloxacin, in the 1980s, the agents assumed a greatly expanded clinical role because of their broad antimicrobial spectrum of action, improved pharmacokinetic properties, and more acceptable safety profile. Although the pharmacokinetics and efficacy of the drugs have improved significantly, a major area of continued emphasis is to further reduce the frequency and severity of adverse events and drug-drug interactions. Older agents such as ciprofloxacin and ofloxacin are still extensively prescribed, but the focus of this article is on the newer fluoroquinolones (levofloxacin and other drugs that have been approved or have been under investigation since approximately 1997).

Anti-Infective Agents↗
PubMed2000

Management of protease inhibitor-associated diarrhea.

Diarrhea is a common and often inadequately treated complication in patients with human immunodeficiency virus infection. Diarrhea has a significant impact on quality of life (QOL) and can contribute to malnutrition, weight loss, immunosuppression, and mortality. In addition, diarrhea may have a significant impact on compliance with antiretroviral therapy; however, this impact has not been adequately assessed. Medications, including protease inhibitors (PIs), are recognized as a common cause of diarrhea. Treatment of PI-associated diarrhea is largely nonspecific; most of the available literature is published only in abstract form and is based primarily on retrospective and survey data. Agents for which some efficacy has been shown for treatment of PI-associated diarrhea include oat bran, psyllium, loperamide, calcium carbonate, SP-303, and pancrelipase. Practitioners and patients need to work together to determine which treatment modality is appropriate based on efficacy, cost, and lifestyle. Management of diarrhea is crucial to improving QOL, controlling weight loss, and enhancing overall efficacy of antiretroviral therapy.

Antidiarrheals↗
PubMed2000

Fludrocortisone for the treatment of heparin-induced hyperkalemia.

OBJECTIVE: To report the use of fludrocortisone for heparin-induced hyperkalemia and to briefly review the available literature relating to heparin-induced hyperkalemia. CASE SUMMARY: A 34-year-old African-American man was admitted to the hospital for pneumococcal pneumonia and sepsis. His hospital course was complicated by the development of acute respiratory distress syndrome, severe sepsis, acute renal failure, placement of a tracheostomy, and recurrent nasopharyngeal bleeding. The patient also developed a subclavian vein thrombosis with extension to the cephalic and basilic veins secondary to placement of a pulmonary artery catheter; anticoagulation with heparin was required. On day 9 of heparin therapy, the patient developed symptomatic hyperkalemia refractory to conventional therapies. Oral fludrocortisone 0.1 mg/d was initiated with resolution of the hyperkalemia within 24 hours despite the continued administration of heparin. DATA SOURCES: A MEDLINE (1966-October 1999) search was performed to identify case reports and clinical trials discussing heparin-induced hyperkalemia or the use of fludrocortisone for hyperkalemia. DISCUSSION: Heparin has the potential to induce hyperkalemia by several mechanisms, including decreased aldosterone synthesis, reduction in number and affinity of aldosterone II receptors, and atrophy of the renal zona glomerulosa. Fludrocortisone promotes potassium excretion by its direct actions on the renal distal tubules. In this patient, fludrocortisone resulted in a significant and rapid decrease in serum potassium even with continued heparin administration and acute renal failure. CONCLUSIONS: This case suggests that fludrocortisone is a reasonable alternative therapy for patients with hyperkalemia secondary to heparin therapy when the continued administration of heparin is necessary.

Adult↗
PubMed2000

Pharmacokinetics of intravenous trovafloxacin in critically ill adults.

The pharmacokinetic disposition of numerous antimicrobial agents is altered in critically ill patients. Pharmacokinetics of trovafloxacin, a fluoroquinolone indicated specifically for severe, life-threatening infections in the intensive care unit, have not been well studied in this population. We characterized the pharmacokinetic disposition of trovafloxacin after administration of alatrofloxacin, the intravenous prodrug, in critically ill adults. Seven patients (3 men, 4 women; mean +/- SD age 59.4 +/- 20.6 yrs; baseline aspartate aminotransferase [AST]/alanine aminotransferase [ALT] 66.0 +/- 40.6/51.5 +/-37.5 IU/L; median Acute Physiology and Chronic Health Evaluation [APACHE II] score 27, range 15-32) were studied at estimated steady state. Calculated (mean +/- SD) half-life, clearance at steady state, and volume of distribution in all patients were 10.9 +/- 1.8 hours, 161.3 +/- 41.1 ml/minute, and 1.4 +/- 0.4 L/kg. In patients receiving 300 mg, maximum concentration, minimum concentration, and area under the curve from 0-24 hours were 3.6 +/- 0.5 mg/L, 0.6 +/- 0.3 mg/L, and 34.2 +/- 10.6 mg x hr/L, respectively. These results are consistent with published values in other patient populations, indicating that trovafloxacin pharmacokinetics are not substantially altered in critically ill patients with normal or mildly impaired hepatic function.

Adult↗
PubMed1999

Stability of valacyclovir hydrochloride in extemporaneously prepared oral liquids.

The stability of valacyclovir hydrochloride in three commonly used syrups was studied. Triplicate suspensions of valacyclovir (from caplets) in Ora-Sweet (Paddock Laboratories), Ora-Sweet SF (Paddock), and Syrpalta Humco Laboratory) syrups were extemporaneously compounded to yield a final concentration of valacyclovir 50 mg/mL (as the hydrochloride salt). The nine suspensions were stored at 4 degrees C in amber glass bottles. At intervals up to 60 days, the liquids were visually inspected for color change, cloudiness, gas formation, and precipitation, and samples were assayed in duplicate for valacyclovir concentration by stability-indicating high-performance liquid chromatography. Also tested were pH, particle size, and microbial growth. During the first 21 days of storage, mean valacyclovir concentrations in all liquids were >90% of the initial concentration, but concentrations were <90% by day 21 in some individual samples of suspensions prepared with Ora-Sweet and Ora-Sweet SF. Mean valacyclovir concentrations in the Syrpalta-based suspensions met the 90% cutoff for at least 35 days. Solution pH and particle size remained unchanged in all liquids through day 60, and there were no changes in physical appearance. There was no evidence of microbial growth on the days when microbial growth was tested (0 and 28). Valacyclovir 50 mg/mL (as the hydrochloride salt) in three oral liquids stored in amber glass bottles at 4 degrees C was stable for at least 21 days when prepared with two of three syrups and for at least 35 days when prepared with the third syrup. All the liquids were free of microbial growth for at least 28 days.

Acyclovir↗
PubMed1999

Valacyclovir inhibits recovery of ocular HSV-1 after experimental reactivation by excimer laser keratectomy.

PURPOSE: The goal of this was to determine whether the systemic administration of valacyclovir (Valtrex) would reduce ocular shedding of herpes simplex virus 1 (HSV-1) after excimer laser ablation in the New Zealand rabbit latency model. METHODS: The in vitro 50% inhibitory concentration (IC50) of HSV-1 W strain was determined by using a plaque-reduction assay to verify its sensitivity to acyclovir. Forty-seven NZW rabbits latently infected with HSV-1 W strain were divided into four groups: I, 50 mg/kg/day valacyclovir; II, 100 mg/kg/day valacyclovir; III, 150 mg/kg/day valacyclovir; and IV, saline control. One half of the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with one dose before excimer laser keratectomy. HSV-1 ocular shedding was determined from eye cultures for 7 days after treatment. RESULTS: The IC50 for HSV-1 W was determined to be 2.9 microg/ml. The administration of both 100 mg/kg/day (group II) and 150 mg/kg/day (group III) of valacyclovir significantly reduced the number of eyes from which latent HSV-1 was recovered compared with the control group. There was no difference between the control group and group I (50 mg/kg/day valacyclovir). However, all three valacyclovir dosages significantly reduced the total number of HSV-1 shedding days compared with the control group, and 100% HSV-1 TG latency was demonstrated for all four groups. CONCLUSION: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding in a dose-dependent manner after excimer laser keratectomy in the NZW rabbit latency model.

Acyclovir↗
PubMed1999

Pharmacokinetics of a clarithromycin suspension administered via nasogastric tube to seriously ill patients.

The pharmacokinetics of clarithromycin and its 14-(R)-hydroxylated metabolite were studied on two separate occasions after nasogastric administration of 500 mg of a clarithromycin suspension to 16 seriously ill adults in an intensive care unit. The clarithromycin suspension appeared to be adequately absorbed, and the pharmacokinetics of neither clarithromycin nor 14-(R)-hydroxyclarithromycin differed significantly between the two dosing periods. No substantial differences in pharmacokinetics were observed compared to previously published studies of other adult populations. Minimal intrapatient variability of pharmacokinetic parameters was observed in these seriously ill patients.

Adult↗
PubMed1999

The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol.

This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis machine; Fresenius F80B dialyzer; median blood flow rate 400 ml/min; dialysate flow rate 600 ml/min; median hemodialysis time 3.5 h). The seventh subject, being treated for tuberculosis (TB), was studied with his usual regimen. Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using high-performance liquid chromatography (HPLC) (INH, RIF) and gas chromatography/mass spectrometry (GC/MS) (PZA, EMB) methods. Median recoveries of drug in dialysate were 9% (INH), 4% (RIF), 45% (PZA), and 2% (EMB) of the doses administered. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during hemodialysis were 124 (INH), 40 (RIF), 270 (PZA), and 46 (EMB) ml/min. INH, RIF, and EMB were not significantly removed by hemodialysis. PZA is significantly dialyzed and should be dosed after hemodialysis.

Adult↗
PubMed1999

The effect of hemodialysis on cycloserine, ethionamide, para-aminosalicylate, and clofazimine.

STUDY OBJECTIVES: Determine hemodialysis clearances of the second-line antitubercular drugs cycloserine (CS), ethionamide (ETA), para-aminosalicylate (PAS), and clofazimine (CFZ). DESIGN: Open-label, pharmacokinetic study SETTING: Outpatient long-term hemodialysis unit PARTICIPANTS: Eight long-term hemodialysis patients Interventions: Single oral doses of CS, 500 mg, ETA, 500 mg, PAS, 4,000 mg, and CFZ, 200 mg, were given 2 h (4 h for PAS) prior to hemodialysis (median blood flow rate, 400 mL/min; median dialysate flow rate, 600 mL/min; median hemodialysis time, 3.5 h). MEASUREMENTS AND RESULTS: Arterial and venous serum samples were collected at the beginning and end of hemodialysis, and hourly during hemodialysis. Dialysate fluid was collected for the duration of hemodialysis. All samples were assayed for drug concentrations using validated high-performance liquid chromatography (for ETA and PAS), capillary electrophoresis (for CS), and colorimetry (for CFZ). Dialysate samples were analyzed for acetyl-PAS. Median recoveries of drug in dialysate were 56% (CS), 2.1% (ETA), 6.3% (PAS parent compound), and 0% (CFZ) of the doses administered. Acetyl-PAS was dialyzed to a greater extent than its parent compound. Median hemodialysis clearances calculated by dividing the amount recovered in dialysate by the serum area under the curve during dialysis were 189 (CS), 58 (ETA), 206 (PAS), and 0 (CFZ) mL/min. CONCLUSIONS: ETA, CFZ, and PAS were not significantly dialyzed. CS is significantly removed by hemodialysis and should be dosed after hemodialysis.

Adolescent↗
PubMed1997

Stability of sumatriptan succinate in extemporaneously prepared oral liquids.

The stability of sumatriptan succinate in extemporaneously prepared oral liquids was studied. Suspensions of sumatriptan (as the succinate salt) in Ora-Sweet, Ora-Sweet SF, and Syrpalta syrups (Paddock Laboratories and Humco Laboratory) were extemporaneously compounded to produce a sumatriptan concentration of 5 mg/mL. Each suspension was prepared in triplicate. The suspensions were stored at 4 degrees C in amber glass bottles for 60 days. Two 1-mL samples were removed from each bottle initially and on days 2, 7, 14, 21, 28, 35, and 60. Sumatriptan concentrations were determined by high-performance liquid chromatography. The samples also underwent visual inspection and microbial testing. The mean concentration of sumatriptan in all suspensions remained above 90% of the initial concentration for up to 21 days. By day 28, the sumatriptan concentration of all suspensions had decreased to less than 90% of the initial concentration. None of the suspensions had microbial growth up to day 28, and there were no visible changes in the suspensions throughout the study period. Sumatriptan 5 mg/mL (as the succinate salt) in three oral suspensions was stable for up to 21 days when stored without light at 4 degrees C.

Administration, Oral↗