Biomedical subjects

C H Ballow

Publications and source records attributed to C H Ballow.

28 records · Page 2Linked to original sources

PubMed1992

Azithromycin: the first azalide antibiotic.

OBJECTIVE: To discuss the chemistry, mechanism of action, spectrum of activity, pharmacokinetics, clinical trials, adverse-effect profile, drug interactions, and dosage guidelines of azithromycin, the first azalide antibiotic. DATA SOURCES: Pertinent literature published between 1988 and the present was identified via a MEDLINE search. Of 77 articles retrieved, 37 have been referenced. STUDY SELECTION: Azithromycin is a new agent, and as such, limited data regarding this drug are available in the literature. We evaluated all pharmacokinetic, microbiologic, and basic science articles pertaining to azithromycin, and reviewed the clinical efficacy trials that we believed were of good quality for each indication for which azithromycin has received approval to date. Comparative clinical trials involving large numbers of patients, clinical outcome assessments, and recommendations for azithromycin use are included. DATA SYNTHESIS: Azithromycin is a macrolide derivative and the first of the 15-membered ring azalide class of antimicrobials. Although its mechanism of action and susceptibility to resistance are similar to those of the macrolide antibiotics, azithromycin's extended spectrum of activity includes gram-positive and gram-negative organisms, as well as atypical pathogens. Azithromycin is stable at gastric pH and has an absolute bioavailability of approximately 37 percent following oral administration. Although its serum concentrations are typically low, the drug concentrates to a high degree in tissue. Azithromycin is cleared primarily by the biliary and fecal routes; its serum half-life is in excess of 60 hours. Several clinical trials have proven that a 5-day course of azithromycin administered once a day is equally efficacious to a 7- to 14-day course of other commonly used oral antimicrobials, administered two to four times a day, for the treatment of upper and lower respiratory tract and skin and skin-structure infections. Urethritis and cervicitis caused by chlamydia are treated with a single 1-g dose. Trials have shown azithromycin's adverse-effect profile to be equal or even superior to that of other agents, with only 0.7 percent of patients discontinuing therapy versus 2.6 percent for comparable drugs. CONCLUSIONS: Azithromycin represents a significant improvement in the treatment of selected community-acquired infections. Although this agent may revolutionize the treatment of sexually transmitted diseases caused by chlamydia, it also should impact the management of respiratory tract and skin and skin-structure infections. Because of its unique pharmacokinetics and excellent adverse-effect profile, patient compliance should be greatly enhanced compared with other commonly used oral antimicrobials. Azithromycin's primary role in the near future will be in the community setting. Although its use in the hospital may be limited, this drug will be a convenient therapeutic option to have on hand in the emergency room and outpatient clinic. Azithromycin may also be used in the future to treat opportunistic infections in immunocompromised patients.

Azithromycin↗

PubMed1992

Trends in antibiotic utilization and bacterial resistance. Report of the National Nosocomial Resistance Surveillance Group.

The increasing use of "third-generation" cephalosporins has been associated with a rising prevalence of resistant bacteria possessing type-I beta-lactamases. At Millard Fillmore Hospital (Buffalo, New York), we observed an unusually high occurrence of multiply resistant Enterobacter cloacae infections, especially in the intensive care unit. Susceptibilities were found to have declined substantially from 1988 to 1990, most notably for ceftazidime and mezlocillin, which decreased from 83% to 54% and from 85% to 64%, respectively. During the same period, there was a substantial increase in the use of ceftazidime and a decline in the use of the broad-spectrum penicillins. The latter drugs had been used in combination with an aminoglycoside as the primary empiric antibiotic therapy for nosocomial infections. This change in antibiotic-prescribing patterns was coincident with the decline in E. cloacae susceptibility, and therefore the emergence of multiply resistant E. cloacae was probably a direct consequence of the increased prescribing of ceftazidime. The experience at out institution led to the formation of the National Nosocomial Resistance Surveillance Group (NNRSG) to determine whether this antibiotic use-mediated resistance was a nationwide phenomenon. Clinical pharmacists and medical microbiologists were recruited and asked to complete a survey of hospital demographics, antibiotic purchases (between the beginning of 1988 and the third quarter of 1990), and bacterial susceptibilities of six representative organisms to 12 commonly used antibiotics (primarily broad-spectrum penicillins and cephalosporins). Evaluable data were obtained from 18 hospitals varying widely in bed capacity, antibiotic use, and geographic location.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

PubMed1991

Tissue-directed pharmacokinetics.

Azalide antibiotics demonstrate pharmacokinetics distinct from all antibacterial agents in common use. Following oral absorption, conventional oral antibiotics diffuse through serum and interstitial compartments and are eliminated rapidly. A minimal to moderate degree of intracellular penetration may be observed. The pharmacokinetics of azithromycin, the first azalide, are characterized by a rapid and extensive movement of the drug from the serum into intracellular compartments. A dynamic equilibrium exists between the intracellular, interstitial, and serum compartments, with predominant flux into tissue sites. Azithromycin is concentrated to a high degree within phagocytes and transported by chemotactic mechanisms to the site of infection. High concentrations of azithromycin are found in pulmonary, genital, and lymphatic tissues. Azithromycin's serum levels decline in a polyphasic manner with a terminal half-life of approximately 60 hours. These kinetics allow azithromycin to be administered once daily. It is predicted that after drug administration for 5 days, therapeutic levels of azithromycin will be maintained at the tissue sites of infection for an additional 4-7 days. Consideration of the extravascular pharmacodynamics of azithromycin is necessary when making predictions regarding its therapeutic application.

Animals↗

PubMed1991

Seizure activity associated with imipenem use: clinical case reports and review of the literature.

Two patients with multiple organ systems failure developed seizures after receiving imipenem/cilastatin (I/C) despite dose adjustment for poor renal function. Neither patient had a past history of seizures, nor had experienced seizures after receiving high doses of other beta-lactam antibiotics. Simple dose adjustment of I/C based on low creatinine clearances may not be adequate to prevent seizures.

Aged↗

PubMed1984

Inhibition of mixed-function oxidation in perfused rat liver by fluoroacetate treatment.

The effect of fluoroacetate, an inhibitor of the citric acid cycle, on the mixed-function oxidation of p-nitroanisole in isolated perfused livers from fed rats was studied. The citric acid cycle was inhibited by injection of 5 mg/kg sodium fluoroacetate into rats 3 hr prior to liver perfusion experiments. Inhibition of the citric acid cycle was marked by accumulation of citrate (5-fold) and decreases in rates of glycolysis and glycogenolysis by 50-90%. Fluoroacetate treatment inhibited mixed function oxidation in the perfused liver by about 50% without affecting p-nitroanisole O-demethylation by isolated microsomes. Fluorocitrate, at concentrations up to 50 microM, did not inhibit microsomal p-nitroanisole O-demethylation in vitro. These data support the hypothesis that mixed-function oxidation in intact hepatocytes is dependent upon reducing equivalents generated via the citric acid cycle.

Animals↗

PubMedDate not supplied

Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory.

Rapid reporting of culture and susceptibility data is the first of several important steps in the successful management of infected patients. As has been said many times, rapidly reported data are of little value unless the patient directly benefits. Benefit requires better overall communication and an action plan linked to timely use of these results. In 1989 the Millard Fillmore Hospital Antibiotic Review Committee developed and implemented a prototype approach to hospital wide antimicrobial management. The formulary was revised and the drug use evaluation process modified to enhance effectiveness and to lower the cost of therapy and inventory. Clinical pharmacy antimicrobial agent management specialists were then recruited to individualize patient treatments to the isolated pathogens in conjunction with the Division of Infectious Diseases. To provide the clinical pharmacy specialists with rapid and clinically useful information, a real-time computer link was created between the pharmacy (antibiotic orders) and the microbiology laboratory (culture results). Customized software was implemented to screen all patients automatically for mismatches between pathogens and drugs, or to screen for doses inappropriate to minimum inhibitory concentration or renal function. Special attention was paid to identification of opportunities to target a more appropriate narrow-spectrum regimen after culture results became available. Changes in antimicrobial regimen or dosage were made by contacting the prescribing physician. Over 90% of the recommended changes were made, and virtually all changed regimens had satisfactory clinical outcome. Real dollar expenditures for antimicrobial agents declined by > $200,000 per year. Prior to the institution of this computerized clinical management strategy, antimicrobial purchases were rising yearly at the rate of 12%-15%. The combined efforts of clinical pharmacy, microbiology, and infectious disease personnel successfully optimized antimicrobial therapy on a hospital wide basis. Antimicrobial agent optimization improved patient outcome, and the cost savings more than covered the costs of the program personnel and software.

Anti-Bacterial Agents↗

PubMedDate not supplied

Multi-laboratory assessment of the linezolid spectrum of activity using the Kirby-Bauer disk diffusion method: Report of the Zyvox Antimicrobial Potency Study (ZAPS) in the United States.

The in vitro activity of linezolid against common Gram-positive pathogens was compared to that of penicillin or ampicillin or oxacillin (depending upon genus), cefazolin, erythromycin, clindamycin, quinupristin/dalfopristin, levofloxacin, nitrofurantoin and vancomycin by disk diffusion methods. One hundred and six centers (31 states in US) tested recent clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecium, E. faecalis, Streptococcus pneumoniae, and other streptococci. Testing was conducted using the standardized disk diffusion method and concurrent quality control testing was performed. Strains with linezolid zone diameters of < or = 20 mm were requested for referral to the microbiology monitor for confirmation. A total of 3,100 isolates (97% compliance) were tested. Susceptibility (zone diameters, > or = 21 mm) of staphylococci and streptococci to linezolid was reported in 100% and 99.4% of staphylococci and streptococci, respectively. Susceptibility (zone diameters, > or = 23 mm) of enterococci to linezolid was 96.0% with only three isolates (0.4%) reported as resistant (zone diameters, < or = 20 mm; unconfirmed). Among a total of nine isolates (0.3%) reported to have zone diameters 20 mm, six were not submitted for further testing, two were contaminated with Gram-negative bacilli and one was determined to be linezolid-susceptible. There were no differences in linezolid susceptibility in the vancomycin- or oxacillin- or penicillin-resistant subsets of strains. This susceptibility pattern for US medical centers is indicative of the excellent and nearly complete in vitro activity against the key Gram-positive pathogens for which linezolid has received US Food and Drug Administration indications for clinical use.

Acetamides↗

PubMedDate not supplied

Mathematical examination of dual individualization principles (II): The rate of bacterial eradication at the same area under the inhibitory curve is more rapid for ciprofloxacin than for cefmenoxime.

OBJECTIVE: To compare two antibiotics at equal ranges of area under the inhibitory curve (AUIC) exposure to determine if the rate of bacterial eradication differed between these antibiotics. DESIGN: Retrospective comparison of two previously collected studies of similar patients with nosocomial pneumonia. SETTING: Hospitalized patients, most intubated in critical care units with nosocomial pneumonia. PARTICIPANTS: Patients treated with either i.v. ciprofloxacin (n = 74) or the i.v. third-generation cephalosporin cefmenoxime (n = 43) were compared for their length of treatment required to eradicate bacterial pathogens from their respective infection sites, using serial cultures from the site of infection. All patients were also assessed for clinical outcomes. Serum samples were obtained to evaluate individual patient antibiotic pharmacokinetics, which were used to model pharmacodynamics of response. The HPLC assay used for each antibiotic had interday coefficients of variation < 10 percent. Serum concentration versus time profiles were fit using the computer program ADAPT II to determine pharmacokinetic parameters for each patient. The primary drug exposure measure that related to response was the AUIC, calculated as steady-state AUC0-24/minimum inhibitory concentration. RESULTS: AUIC values in the patients ranged from 6.0 to more than 7000, yet the AUIC value was highly predictive of time to bacterial eradication (p < 0.001). Although more than 75 percent of patients eventually achieved eradication of pathogens from tracheal aspirate cultures, ciprofloxacin and cefmenoxime differed significantly in the time required to sterilize these cultures. At appropriate AUIC values (> 250) for ciprofloxacin, the median time to eradication was two days, while cefmenoxime (also at AUIC values > 250) required six days to achieve the same result. CONCLUSIONS: We conclude that the more rapid in vitro bacterial killing, which is characteristic of ciprofloxacin at optimal AUIC values, can manifest in vivo as more rapid clearance of bacteria from the respiratory tract of patients, even when both agents are controlled for initial antibacterial exposure (i.e., same AUIC).

Anti-Bacterial Agents↗

PubMedDate not supplied

Cost considerations in oral antibiotic therapy.

The total cost of antibiotic treatment may be computed from basic treatment and indirect costs. Basic treatment costs represent the product of the per-dose acquisition cost and the number of doses. Agents with a high per-dose acquisition cost and an infrequent (eg, once daily), short duration of therapy may have lower total costs than agents with a low per-dose acquisition cost and a high-frequency (eg, four times daily), long-duration regimen. Indirect cost reflects expenditures associated with noncompliance, treatment failure, adverse events, and drug interactions. These costs result, in turn, from additional office visits, treatment with alternative or additional medications, hospitalization, and lost productivity. Older agents, though likely to have lower acquisition costs, may have reduced efficacy against clinically important pathogens, side effects, drug interactions, and the requirement for multiple daily doses and long dosage regimens--factors that may increase the probability of poor outcome and the overall treatment cost. Newer broad-spectrum agents are effective and generally well tolerated and may have fewer drug interactions; however, most require long and relatively complex dosage regimens. These limitations increase the basic treatment cost and influence indirect costs through negative effects on patient compliance. Broad-spectrum antibiotics with low acquisition costs, simple dosing regimens, and relatively favorable safety and tolerability profiles may provide benefits in the treatment of common infections.

Anti-Bacterial Agents↗

PubMedDate not supplied

Prospective validation of an optimal sparse plasma-sampling strategy for estimating ciprofloxacin pharmacokinetics.

Data obtained from 23 critically ill patients treated with intravenous ciprofloxacin in two clinical trials were used to validate prospectively a previously developed maximum a posteriori (MAP)-Bayesian estimator and optimal plasma-sampling strategy (OSS). Dosages ranged from 200 mg every 12 hours to 400 mg every 8 hours. Each patient had 8-16 samples taken, either as large gold standard sampling sets or as a mix of gold standard sets and OSSs. The MAP-Bayesian estimator used a two-compartment model and identified apparent volumes of distribution of the central and peripheral compartments, distributional clearance, and the slope and intercept of the relationship between creatinine clearance and total body clearance. Fit parameters were used to derive the apparent volume of distribution at steady state and the 24-hour area under the curve. All parameters derived from the OSS using the MAP-Bayesian estimates matched up almost identically to those obtained from modeling the gold standard sets. There was no systematic bias, and good precision was seen among all the parameters. These data demonstrate the usefulness and validity of the current OSS and MAP-Bayesian estimator, and provide further evidence of the utility of optimal sampling theory.

Adult↗