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Biomedical subjects

L H Danziger

Publications and source records attributed to L H Danziger.

At least 37 records · Page 2Linked to original sources
PubMed1997

In vitro activity of clarithromycin alone and in combination with ciprofloxacin or levofloxacin against Legionella spp.: enhanced effect by the addition of the metabolite 14-hydroxy clarithromycin.

Clarithromycin is metabolized to an active metabolite, 14-hydroxy clarithromycin. These compounds have demonstrated excellent in vitro activity against Legionella species, with both agents having significantly lower MICs than erythromycin. Using a checkerboard assay, the activity of clarithromycin and its hydroxy metabolite, alone and in combination, was examined against 41 Legionella organisms. The activity of clarithromycin and 14-hydroxy clarithromycin, in a 2:1 ratio, plus ciprofloxacin or levofloxacin was also determined. Activity of the antibiotic combinations was determined by calculating the fractional inhibitory concentration index. An agar dilution method using buffered charcoal yeast extract media was used for susceptibility and synergy testing. An inoculum of 10(4) CFU/spot was used, with all plates incubated at 35 degrees C for 48 h. The MIC90 for clarithromycin or 14-hydroxy clarithromycin alone was 0.5, versus 0.25 microgram/mL for the combination. Additive effects were observed with clarithromycin and its hydroxy metabolite for 61% of the Legionella species, with fractional inhibitory concentration indices ranging from 0.63 to 1.25. The 14-hydroxy metabolite significantly increased the activity of both fluoroquinolone/clarithromycin combinations. Based on these data, in vitro susceptibility testing of agents such as clarithromycin should be reevaluated to account for the activity of active metabolites.

Anti-Bacterial Agents↗
PubMed1997

Pharmacokinetics and pharmacodynamics of two multiple-dose piperacillin-tazobactam regimens.

The pharmacokinetics and pharmacodynamics of two multiple-dose regimens of piperacillin-tazobactam (3.375 g every 6 h and 4.5 g every 8 h) were evaluated at steady state for 12 healthy adult volunteers. Inhibitory and bactericidal activities for the two regimens were determined with five American Type Culture Collection (ATCC) organisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis). The percentage of time that plasma concentrations remained above the MIC (T > MIC) for each organism and dosage regimen was calculated. Areas under the inhibitory (AUIC0-24) and bactericidal activity (AUBC0-24) curves were calculated with the trapezoidal rule by using the reciprocal of the inhibitory and bactericidal titers determined for each dosage regimen. In order to assess the validity of predicted measures of bactericidal (AUC0-24/MBC) and inhibitory (AUC0-24/MIC) activity to determine bacteriological response to beta-lactam antimicrobial agents, AUC0-24/MBC and AUC0-24/MIC values were compared with measured AUBC0-24 and AUIC0-24 values. Total body clearance values were equivalent for piperacillin (183.96 +/- 22.66 versus 181.72 +/- 19.54 ml/min/1.73 m2, P > 0.05) and tazobactam (184.71 +/- 19.89 versus 184.87 +/- 18.35 ml/min/1.73 m2, P > 0.05) following the administration of the 3.375-g-every-6-h and 4.5-g-every-8-h dosages, respectively. Comparison of area under the plasma concentration-time curve (AUC0-24) for piperacillin (967.74 +/- 135.56 microg x h/ml versus 978.88 +/- 140.96 microg x h/ml) and tazobactam (120.14 +/- 15.78 microg x h/ml versus 120.01 +/- 16.22 microg x h/ml) revealed no significant differences (P > 0.05) between the 3.375-g-every-6-h and 4.5-g-every-8-h regimens, respectively. Both regimens provided T > MIC values of > 60% for all organisms tested. Measured values of bactericidal (AUBC) and inhibitory (AUIC) activity were significantly different (P < 0.05) from predicted values (AUC0-24/MBC and AUC0-24/MIC) for all organisms studied with the exception of the bactericidal activity for P. aeruginosa and S. aureus. Additionally, ATCC organisms possessing the same MICs and MBCs exhibited great differences in measured AUBC0-24 and AUIC0-24 values. Reasons for this difference may be inherent differences in organism specific susceptibility.

Adult↗
PubMed1997

Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.

Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.

Adult↗
PubMed1997

Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers.

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.

Administration, Oral↗
PubMed1997

In vitro synergy testing of clarithromycin and 14-hydroxyclarithromycin with amoxicillin or bismuth subsalicylate against Helicobacter pylori.

The activity of clarithromycin-14-hydroxyclarithromycin (2:1 ratio) and bismuth subsalicylate or amoxicillin against Helicobacter pylori was determined by the checkerboard technique in vitro. Clarithromycin-14-hydroxyclarithromycin and amoxicillin resulted in additive effects in 7 of 22 isolates, compared to 14 of 22 isolates when bismuth subsalicylate was substituted for amoxicillin. Synergy was not demonstrated and is probably not responsible for the clinical success of treatment combinations containing clarithromycin.

Amoxicillin↗
PubMed1997

Comparison of charcoal- and starch-based media for testing susceptibilities of Legionella species to macrolides, azalides, and fluoroquinolones.

We compared growth characteristics of 46 Legionella strains grown on buffered charcoal yeast extract alpha (BCYE alpha) agar and buffered starch yeast extract (BSYE) agar and MICs of macrolides, azalides, and fluoroquinolones for these organisms. Growth was poor and not reproducible on BSYE agar. Growth was excellent on BCYE alpha, and MICs were easy to interpret. BCYE alpha is superior to BSYE for testing susceptibilities of Legionella species by agar dilution.

Anti-Bacterial Agents↗
PubMed1996

Therapeutic modalities for mechanical cleansing of the colon.

Mechanical cleansing of the colon is an accepted standard of practice prior to colon surgery, and endoscopic and radiographic procedures. Cleansing the bowel prior to these procedures increases the accuracy of the diagnostic procedures and decreases the morbidity and mortality following surgery, where fecal contamination is a concern. Mechanical cleansing agents are sometimes used for acute constipation, but because of the extent and harshness of the evacuation they induce, and because of their adverse effects, they are not used for long-term management of constipation. Dosages vary among products, procedures, and individuals. Manufacturer guidelines should be consulted for proper dosing and administration.

Bisacodyl↗
PubMed1996

In vitro synergy testing of macrolide-quinolone combinations against 41 clinical isolates of Legionella.

Combination antimicrobial therapy against Legionella species has not been well studied. Several quinolones have activity against Legionella strains, which prompted this in vitro search for a synergistic combination with the macrolides. By a checkerboard assay, erythromycin, clarithromycin, and azithromycin, each in combination with ciprofloxacin and levofloxacin, were tested for synergy against 46 isolates of Legionella. The agar dilution method was employed using buffered charcoal-yeast extract media. A final inoculum of 10(4) CFU per spot was prepared from 24-h growth of each isolate. Plates were incubated at 35 degrees C for 48 h. Synergy, partial synergy, additive effect, or indifference was observed for all combinations of antibiotics tested. There was no antagonism observed. Synergy occurred to a significantly greater extent for the clarithromycin-levofloxacin (P = 0.0001) and azithromycin-levofloxacin (P = 0.003) combinations versus erythromycin-levofloxacin. The azithromycin-ciprofloxacin combination demonstrated significantly greater synergy than did either erythromycin-ciprofloxacin (P = 0.003) or clarithromycin-ciprofloxacin (P = 0.001). The newer macrolides clarithromycin and azithromycin may be more active in combination with a fluoroquinolone than is erythromycin.

Anti-Bacterial Agents↗
PubMed1995

Bacterial resistance to beta-lactam antibiotics.

The historical development of antibiotic resistance, mechanisms of resistance, classification schemes for beta-lactamases, the clinical relevance of resistance, and approaches to overcoming resistance are reviewed. The promise of eradication of infectious diseases has not been fulfilled, in great part owing to the emergence of antibiotic-resistant organisms. Although genes for bacterial resistance may have existed before the clinical use of antibiotics, selection of new resistant strains is driven by the widespread use of antimicrobials in humans and animals. The most commonly prescribed antimicrobials in the United States are the beta-lactam antibiotics, and the most common mechanism of bacterial resistance to these agents is inactivation by beta-lactamase. The clinical and economic consequences of therapeutic failure and relapse--extended hospital stays, increased morbidity and mortality, and the use of potentially more toxic and costly antimicrobial agents--require new strategies to prevent the spread of resistant organisms and to limit future resistance.

Anti-Bacterial Agents↗
PubMed1995

Piperacillin/tazobactam: a new beta-lactam/beta-lactamase inhibitor combination.

OBJECTIVE: To discuss the antimicrobial activity, pharmacokinetics, clinical efficacy, and adverse effect profile of piperacillin/tazobactam, a new beta-lactan/beta-lactamase inhibitor combination. DATA SOURCES: Literature was identified by MEDLINE search of the medical literature, review of selected references, and data provided by the manufacturer. STUDY SELECTION: In vitro susceptibility data were surveyed from studies following the methods of the National Committee for Clinical Laboratory Standards. Data evaluating clinical efficacy were selected from all published trials and abstracts. Additional information concerning safety, chemistry, and pharmacokinetics was reviewed. DATA SYNTHESIS: The antimicrobial activity of piperacillin is enhanced by addition of tazobactam against gram-positive, gram-negative, and anaerobic bacteria. Tazobactam is active against a broad spectrum of plasmid and chromosomally mediated enzymes and has minimal ability to induce class I chromosomally mediated beta-lactamase enzymes. Piperacillin/tazobactam's expanded activity appears encouraging in the treatment of mixed aerobic and anaerobic infections. Direct comparisons of ticarcillin/clavulanate and piperacillin/tazobactam for the treatment of lower respiratory tract infections showed piperacillin/tazobactam to be clinically superior, and in the treatment of skin and soft tissue infections the 2 agents were comparable. For the treatment of intraabdominal infections, piperacillin/tazobactam was at least as effective as imipenem/cilastatin and clindamycin plus gentamicin. CONCLUSIONS: The combination of tazobactam with piperacillin results in an antimicrobial agent with enhanced activity against most beta-lactamase-producing organisms. Preliminary data indicate that piperacillin/tazobactam has proven clinical efficacy in the treatment of a variety of infections, especially polymicrobic infections.

Bacterial Infections↗
PubMed1994

Frequency, pathogenicity and microbiologic outcome of non-Candida albicans candiduria.

A retrospective review of urine cultures obtained from patients at the University of Illinois Hospital revealed that the frequency of isolation of non-albicans Candida species increased significantly from 1990 to 1991 (p = 0.0003), while the frequency of isolation of Candida albicans species decreased significantly (p = 0.0006). Patients with urine cultures positive for non-albicans Candida species of Torulopsis glabrata during 1991 were identified for review. Sixty-seven patients were eligible for evaluation. Non-albicans candiduria developed in an average of 12 days. Identical fungal species were isolated from the blood following a positive urine culture in only two patients. Twenty patients were treated; candiduria persisted in 9 (45%), while resolution occurred in 11 (55%). The remaining 47 patients were not treated. Non-albicans candiduria persisted in 30 (64%) of these patients and resolved in 15 (32%); in the remaining two patients (4%) the microbiologic outcome was undetermined. The difference in microbiologic outcomes between treated and untreated patients was not significant using the Chi-square test (p = 0.170). Non-albicans candiduria developed rapidly, frequently persisted whether treated or untreated, and rarely progressed to candidemia.

Administration, Intravesical↗
PubMed1994

Continuous infusion of loop diuretics in the critically ill: a review of the literature.

OBJECTIVES: a) To present the pharmacodynamic concepts behind the administration of loop diuretics via continuous infusion; b) to review the clinical trials and reports in critically ill patients that have described this method of drug delivery; and c) to discuss the data. DATA SOURCES: Review of MEDLINE and International Pharmaceutical Abstracts from 1966 to the present. STUDY SELECTION: Study design was not a factor in selecting literature for this review. All studies, case reports, and case series describing infusion of a loop diuretic are included. DATA EXTRACTION: Cited literature was found in peer-reviewed clinical or basic science journals. DATA SYNTHESIS: There is a pharmacodynamic basis for the use of a controlled infusion of the loop diuretics in critically ill patients requiring extensive diuresis. Animal and human volunteer studies have demonstrated a clear improvement in efficiency of diuresis by controlled infusion Clinical studies in critically ill patients have demonstrated an improved diuretic response with a controlled infusion. Adverse effects appear to be minimal, and the amount of drug required for effect is less than the required amount for bolus administration. CONCLUSION: Administration of loop diuretics by continuous intravenous infusion may improve diuresis in critically ill patients who require prompt, controllable diuresis, or who demonstrate "diuretic tolerance" to conventional administration regimens. Despite few, well-designed studies using this method of administration in clinical practice, pharmacodynamic concepts support continuous infusion over bolus administration, including decreased dosage requirements, improved diuretic response and few adverse effects.

Animals↗
PubMed1994

In vivo activity of paromomycin against susceptible and multidrug-resistant Mycobacterium tuberculosis and M. avium complex strains.

Encouraged by in vitro results, we have assessed the in vivo activity of paromomycin (PRM) against Mycobacterium tuberculosis, multidrug-resistant (MDR) M. tuberculosis (resistant to isoniazid, rifampin, and streptomycin), and Mycobacterium avium complex in C57BL/6 mice and their beige counterparts. In all these experiments, PRM was effective in preventing mortality from a mycobacterial infection and was significantly more active than the drug-free control (P < 0.0005) in reducing the CFU relative to the mean log CFU in the lungs, livers, and spleens of infected animals. In the drug-susceptible M. tuberculosis experiment, PRM given at 100 and 200 mg/kg of body weight was significantly less active than isoniazid at 25 mg/kg (P < 0.0005) in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. In the MDR M. tuberculosis experiment, PRM given at 200 mg/kg was effective, relative to the drug-free control, in reducing the mean log CFU of an isolate of M. tuberculosis resistant to isoniazid, rifampin, and streptomycin. In the M. avium complex experiment, PRM given at 200 mg/kg was as effective as amikacin at 50 mg/kg in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. On the basis of our experiments, we believe that PRM has promising activity in vivo in the treatment of infections caused by M. tuberculosis, MDR M. tuberculosis, and M. avium complex.

Animals↗
PubMed1994

Penetration of clarithromycin into lung tissues from patients undergoing lung resection.

The concentrations of clarithromycin and its active principal metabolite, 14-(R)-hydroxy-clarithromycin, were determined in lung tissue obtained during lung resection and compared with concomitant concentrations in plasma. Concentrations of the parent and metabolite were determined by high-performance liquid chromatography. The 15 patients studied were given 500 mg orally every 12 h for a minimum of five doses to achieve steady-state concentrations. The mean concentrations of clarithromycin and 14-(R)-hydroxy-clarithromycin in plasma just prior to the final dose were 1.38 and 0.67 micrograms/ml, respectively, and those 4 h after the final dose (at the time of lung resection) were 1.89 and 0.80 microgram/mL, respectively. The concentrations of the parent and metabolite in lung tissue at the time of lung resection averaged 54.3 and 5.12 micrograms/g, respectively, with a mean calculated ratio of concentrations of the parent to metabolite being 11.3 in lung tissue and 2.4 in plasma. Clarithromycin and its active metabolite are extensively distributed into human lung tissue.

Adolescent↗
PubMed1994

In vitro activities of metronidazole and its hydroxy metabolite against Bacteroides spp.

Metronidazole is metabolized to two major oxidative products: an acid metabolite and a hydroxy metabolite. While the activity of the acid metabolite is negligible, the activity of the hydroxy metabolite is approximately 65% of the activity of the parent drug. Pharmacokinetic studies of metronidazole and its hydroxy metabolite have shown that the MICs of both compounds remain above the MICs for most anaerobic organisms over an 8-h dosing interval. By a checkerboard assay, the combined activities of metronidazole and the hydroxy metabolite were examined against 4 quality control strains of Bacteroides species. Macrobroth tube dilutions were set up with Wilkins-Chalgren broth. Serial twofold dilutions of each agent were performed to achieve final concentrations ranging from 0.06 to 4.0 micrograms/ml. The MICs for Bacteroides fragilis and B. distasonis were 1.0 microgram/ml for both parent drug and metabolite. For B. thetaiotamicron and B. ovatus, the MICs of metronidazole and the hydroxy metabolite were 1.0 and 2.0 micrograms/ml, respectively. Synergy was determined by calculating the fractional inhibitory concentration (FIC) index. The interpretative criteria for the FIC index were as follows: synergy, FIC < or = 0.5; partial synergy, 0.51 to 0.75; indifference, FIC 0.76 to 4.0; and antagonism, FIC > 4.0. Partial synergy was observed for the four anaerobes tested, with FIC indices ranging from 0.63 to 0.75. On the basis of this data, in vitro susceptibilities to agents such as metronidazole may ultimately require reevaluation to account for active metabolites.

Bacteroides↗
PubMed1994

Steady-state pharmacokinetics of cefoperazone and sulbactam in patients with acute appendicitis.

OBJECTIVE: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean +/- SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2 beta), clearance (Cl), and area under the curve (AUC0-t) were 19.8 +/- 8.0 L, 3.97 +/- 1.06 h, 62.6 +/- 16.3 mL/min, and 556.9 +/- 122.0 mg.h/L, respectively. Sulbactam Vssd, t1/2 beta, Cl, and AUC0-t were 34.7 +/- 13.9 L, 1.39 +/- 0.4 h, 288.6 +/- 68.2 mL/min, and 64.8 +/- 24.5 mg.h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2 beta in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.

Acute Disease↗
PubMed1994

Oral antibiotic usage in hospitalized patients.

With the introduction of the fluoroquinolones, oral antibiotic usage is becoming an increasingly important issue. The medical record of 119 patients receiving oral antibiotics at a university hospital were reviewed to examine demographics and patterns of usage. The population was predominantly female and below 50 years of age. Urinary tract infections were most common followed by infections of the respiratory tract and skin and skin structure. The majority of usage was empiric in nature. The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole, cephalexin, and ampicillin/amoxicillin. Monotherapy with an oral agent was observed in 82% of the cases. Intravenous antibiotics were administered prior to oral therapy in 61% of the patients studied. The authors observed a trend from combination intravenous therapy to single-agent oral therapy. Of the patients discharged on an oral antibiotic, 84% received a prescription for the agent originally prescribed for them in the hospital. Tracking of oral antibiotic inpatient use is effective at assessing major trends in usage.

Administration, Oral↗