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Biomedical subjects

M J Rybak

Publications and source records attributed to M J Rybak.

At least 109 records · Page 6Linked to original sources
PubMed1989

Ofloxacin: a review.

Ofloxacin is a new fluorinated quinolone antibiotic with a broad spectrum of activity against a variety of gram-positive and -negative bacteria including Enterobacteriaceae, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. In addition, ofloxacin has significant activity against Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycobacterium tuberculosis and this may give rise to new indications for the class of quinolone antibiotics. Clinical trials to date have demonstrated the efficacy of ofloxacin in the treatment of lower respiratory tract infections, urinary tract infections, and sexually transmitted diseases. Adverse effects to ofloxacin are usually mild and include gastrointestinal, central nervous system, and hypersensitivity reactions. Significant drug interactions with ofloxacin have not been reported.

Animals↗
PubMed1989

Enoxacin: a new fluoroquinolone.

The chemistry, mechanisms of action and resistance, pharmacokinetics, antimicrobial spectrum, clinical efficacy, adverse effects, and drug interactions of enoxacin are reviewed. Enoxacin is a new fluoroquinolone compound structurally related to nalidixic acid. Its antimicrobial spectrum and activity are comparable to those of the fluoroquinolones norfloxacin and ciprofloxacin. It has a broad spectrum of activity against gram-negative and gram-positive microorganisms, but like the other fluoroquinolones it is less active against gram-positive micro-organisms. Anaerobic organisms are generally resistant to enoxacin. It is rapidly and nearly completely absorbed after oral administration and is distributed widely in body fluids and tissues. The drug is predominantly excreted via the kidney, with a relatively long serum elimination half-life of approximately five hours. Serum and urinary concentration of enoxacin exceed the minimum inhibitory concentrations for most gram-negative and many gram-positive pathogens. Clinical trials have shown enoxacin to be effective for the treatment of gonorrhea, cystitis, complicated urinary-tract infections, and skin and skin structure infections. There is some evidence that enoxacin may be useful for treatment of lower-respiratory-tract infections and ear, nose, and throat infections. The most commonly reported adverse effects are mild gastrointestinal and central nervous system symptoms. Concomitant enoxacin and theophylline therapy has been associated with toxic serum concentrations of theophylline. Interactions have also been reported with caffeine, antacids, cimetidine, warfarin, and fenbufen. Enoxacin (Comprecin, Parke-Davis/Warner-Lambert) will be available in 200-, 300-, and 400-mg tablets for oral administration. Enoxacin is usually taken twice daily. A single 400-mg dose is effective therapy for uncomplicated gonorrhea. Since enoxacin, ciprofloxacin, and norfloxacin have many similar properties, formulary decisions involving these agents should be based on the individual institution's need to treat certain types of infections and pathogenic organisms. Enoxacin has been shown to be an effective agent for the treatment of urinary-tract, genital-tract, and skin and soft-tissue infections, including those that currently require injectable antimicrobial agents or that are resistant to conventional therapy.

Animals↗
PubMed1988

Comparative efficacies of imipenem-cilastatin and vancomycin in experimental aortic valve endocarditis due to methicillin resistant Staphylococcus aureus.

Activities of imipenem and vancomycin against methicillin resistant Staphylococcus aureus (MRSA) were compared in vitro and in a rabbit model of aortic valve endocarditis. Against 25 MRSA clinical isolates, imipenem was bacteriostatic (MIC90/MBC90, mg/l 8/32) in vitro while vancomycin was bactericidal (MIC90/MBC90, mg/l 2/4). Rabbit endocarditis was produced with a MRSA isolate against which both drugs were bactericidal. Imipenem-cilastatin had better efficacy than vancomycin by the following criteria, the number of survivors (9/13 vs 7/13), clearance of bacteraemia (9/9 vs 3/7; P = 0.019), sterility of cardiac vegetations (9/9 vs 1/7; P = 0.001) and sterility of distant organs (8/9 vs 2/7; P = 0.035). Thus, imipenem-cilastatin may be a potentially useful alternative agent to vancomycin in the therapy of MRSA endocarditis in the occasional situations when the drug demonstrates in-vitro bactericidal activity against the pathogen. Efficacy against MRSA strains with higher MBCs remains to be proved.

Animals↗
PubMed1988

Effect of norfloxacin on theophylline pharmacokinetics at steady state.

Norfloxacin is a currently marketed fluoroquinolone antibiotic. Other quinolones which are structurally similar to norfloxacin, particularly enoxacin, inhibit theophylline clearance. Since norfloxacin may be administered to patients also receiving theophylline, we studied the effect of norfloxacin on the pharmacokinetics of theophylline in 10 healthy male volunteers. A randomized, crossover study design with a 2-week washout period between treatments was used. Subjects received oral theophylline (200 mg of aminophylline [theophylline ethylenediamine]) three times daily for 4 days either alone or with 400 mg of norfloxacin (orally) twice daily for the same period. Theophylline concentrations in serum were significantly higher (P less than 0.05) at 0, 3, 4, 10, and 12 h following the final dose in the norfloxacin treatment group than in the group receiving only theophylline. However, mean theophylline oral clearance was not significantly different between the two treatments (2.85 +/- 0.68 liters/h without norfloxacin versus 2.56 +/- 0.53 liters/h with norfloxacin [P = 0.08]). Similarly, no significant differences were observed in theophylline half-life (P = 0.11). We conclude that norfloxacin is unlikely to have a clinically significant effect on theophylline disposition in most patients.

Administration, Oral↗
PubMed1988

Inhibition of drug metabolism by quinolone antibiotics.

A number of quinolone antibiotics have been found to reduce the hepatic clearance of coadministered drugs such as theophylline. Enoxacin appears to be the most potent inhibitor, consistently decreasing theophylline clearance by more than 50%, while a single study suggests a similar degree of inhibition with pipemidic acid. Ciprofloxacin and pefloxacin reduce theophylline clearance to a smaller extent (approximately 20 to 30%). However, with ciprofloxacin, larger changes and theophylline toxicity have been reported in some subjects. Norfloxacin, ofloxacin and nalidixic acid appear to have minimal effects on theophylline clearance. Enoxacin and ciprofloxacin have also been found to reduce the clearance of caffeine, while ofloxacin has no effect. Few other substrates have been studied. Enoxacin decreases the clearance of R-warfarin with no effect on S-warfarin. In addition, enoxacin has been reported to reduce the clearance of antipyrine, with no effect on chlorpropamide, glibenclamide (glyburide) or phenytoin. The mechanism of these interactions is largely unexplored. It has been suggested that inhibition may be related to the production of 4-oxoquinolone metabolites; however, this hypothesis has not been confirmed. No unique structural feature has been identified to date which explains differences between these compounds in their propensity to affect drug metabolism. Further studies are needed to evaluate the effects of these drugs on other substrates not yet examined and to assess whether or not inhibition is dose related. Clinically, caution is advised when using a quinolone, particularly enoxacin, pipemidic acid, ciprofloxacin or pefloxacin, in combination with theophylline. Close monitoring of theophylline concentrations is recommended in any patient receiving these drugs. The clinical significance of inhibited metabolism of other substrates remains unclear at present. Until further data are available, clinicians should be aware of the possibility of reduced drug clearance resulting in adverse effects whenever the fluoroquinolones are coadministered with drugs that depend on hepatic metabolism for their elimination.

4-Quinolones↗
PubMed1988

Comparison of serum sampling methods for determining vancomycin dosage regimens.

The predictive ability of a four-point sampling method versus a two-point sampling method for vancomycin was assessed in 11 patients with various staphylococcal infections. All steady-state predictions were based on first-dose pharmacokinetic parameters. The mean vancomycin serum concentrations achieved at 4 and 8 h postinfusion were not significantly different from the predicted concentrations derived from either the four- or two-point method. Also, there was no significant difference between the two methods in predictive ability or accuracy. Both methods underpredicted the steady-state concentration to the same degree, 2.9 micrograms/ml at 4 h and 3.1 micrograms/ml at 8 h, which would appear to be clinically acceptable. A one-compartment pharmacokinetic model, which uses two serum concentrations, appears to be adequate for adjusting vancomycin regimens.

Adult↗
PubMed1987

Spiramycin in the treatment of cryptosporidiosis.

Spiramycin, a macrolide antibiotic, has been advocated for the treatment of cryptosporidiosis. The disease most commonly occurs in patients with AIDS and can be debilitating, as diarrhea and malnutrition may be contributing factors in the death of these patients. Until recently, treatment for cryptosporidiosis has been largely symptomatic. Response rates with drug therapy such as metronidazole, quinidine-clindamycin, and pentamidine have been extremely poor. Although response to spiramycin has appeared promising, there have been several reported cases of treatment failure. Further investigation with the agent is advocated to determine its role in the treatment of cryptosporidiosis.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin.

The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and beta 2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group. Overall, beta 2M elimination was variable in all treatment groups. Although the beta 2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone.

Adolescent↗
PubMed1987

Increased theophylline concentrations secondary to ciprofloxacin.

An 82-year-old man with a history of myasthenia gravis and heart failure was admitted to the hospital with respiratory failure. Aminophylline and eventually theophylline therapy were initiated to improve respiratory status. During the hospital stay, the patient developed a resistant pseudomonal pneumonia. After failure with conventional antibiotics, ciprofloxacin was initiated because of favorable sensitivity and the planned avoidance of aminoglycoside therapy. Seventy-two hours after initiation of ciprofloxacin, the patient's theophylline level rose from a steady-state baseline of 9.8 micrograms/ml to 34.7 micrograms/ml. After the theophylline dose was reduced by approximately 67 percent, the patient's theophylline serum concentration returned to baseline (10 micrograms/ml). Until more data concerning the interaction of theophylline and ciprofloxacin are available, we recommend close monitoring of theophylline serum concentrations in patients receiving concomitant ciprofloxacin.

Aged↗
PubMed1986

Clinical use and toxicity of high-dose tobramycin in patients with pseudomonal endocarditis.

The effects and toxicity of tobramycin were assessed in 26 patients receiving high-dose (approximately 8 mg/kg/d) therapy for pseudomonal endocarditis or conventional-dose (approximately 3 mg/kg/d) therapy for various systemic Gram-negative infections. Patients in the high-dose group received an average of 29.5 g of drug over 49 days and the dosage was adjusted to maintain peak serum concentrations of 15-20 mg/l. In the conventional-dose group, patients received an average of 8.6 g of tobramycin over 26.7 days and the dosage was adjusted to achieve peak concentrations of 4-10 mg/l. Clinical evidence of acute renal failure was not apparent in any patient. Five of seven patients in the high-dose group, for whom audiologic data was available, exhibited loss of hearing sensitivity in the high frequency range, but no patients sustained significant reduction in hearing in the conversational frequency range. Patients receiving high-dose tobramycin do not appear to be at greater risk for development of nephrotoxicity than do patients receiving conventional-dose therapy.

Adult↗
PubMed1986

Individualized adjustment of vancomycin dosage: comparison with two dosage nomograms.

An individualized method of vancomycin dosage adjustment using steady-state serum concentrations was assessed in 50 patients (86 sets of vancomycin serum concentrations). The predictive accuracy of this method was compared with that of two published nomograms (Moellering, Matzke). Peak and trough serum concentrations predicted from previously drawn vancomycin serum concentrations (individualized method) using a one-compartment pharmacokinetic model were compared with measured steady-state peak and trough serum concentrations. Predicted peak and trough serum concentrations were also generated for both the Moellering and Matzke nomograms by using the elimination rate constant derived from each of the respective nomograms and the fixed volume of distribution (0.9 L/kg) assumed by the nomograms, and the actual administered vancomycin dose and dosage interval. These predicted concentrations were also compared with the measured peak and trough concentrations. Statistical measures of bias and precision indicated that the individualized method of dosage adjustment more closely predicted vancomycin serum concentrations following a dosage change than did either of the nomograms. Overall, the Moellering nomogram was the least accurate of the three methods in predicting vancomycin serum concentrations, and this nomogram should not be used to titrate vancomycin dosages in a clinical setting. Adjustment of vancomycin dosages should be individualized based on pharmacokinetic data derived from measured serum concentrations. In situations where quantitative analysis of vancomycin concentrations is not available, the Matzke nomogram appears to be a reasonable method of adjusting vancomycin dosages.

Adult↗
PubMed1986

Monitoring vancomycin therapy.

Vancomycin is an effective and widely used antistaphylococcal antibiotic. Despite several decades of use, however, our knowledge of the toxicologic and pharmacokinetic properties of vancomycin remains incomplete. This review summarizes current information regarding the adverse reactions and pharmacokinetics of vancomycin. Although there have been reports of side effects with vancomycin, these effects tend to be infrequent, easily managed, and reversible. Several methods for adjustment of vancomycin therapy have been recommended. The relationship between serum concentrations of vancomycin and the occurrence of ototoxicity or nephrotoxicity has not been well established. However, because of large interpatient variations in pharmacokinetic parameters, it seems preferable to individualize vancomycin therapy based on serum concentration data.

Adult↗
PubMed1986

Hematological effects associated with beta-lactam use.

Beta-lactam antibiotics have continued to be the mainstay of antiinfective treatment. Newer agents, such as the third-generation cephalosporins or ureidopenicillins, have the advantage of a broader antimicrobial spectrum and improved pharmacokinetics. The beta-lactams are often promoted as alternatives to more toxic antibiotic regimens. However, several of the beta-lactams have been shown to produce hematological effects, some of which can be life threatening. The primary hematological effects appear to be inhibition of normal platelet function and the coagulation cascade, which is reflected by changes in bleeding times and increases in prothrombin time and activated partial thromboplastin time, respectively. Although not all patients will develop bleeding problems associated with these agents, close monitoring of patients with risk factors for bleeding and dosage adjustments may help to avert these drug-induced hematological problems.

Anti-Bacterial Agents↗