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Biomedical subjects

M H Adelman

Publications and source records attributed to M H Adelman.

12 recordsLinked to original sources
PubMed1997

Changing the infection control paradigm from off-line to real time: the experience at Millard Fillmore Health System.

In 1993, several departments at Millard Fillmore Health System joined efforts to initiate a new approach to infection control. The main emphasis of this program is to move infection control to a real-time mode to manage patient outcomes daily. The principal objective was to decrease the number of nosocomial infections by 10%, with a particular emphasis on surgical-site infections. Besides real-time surveillance, we are critically evaluating several aspects of the management of nosocomial infections. High-level computer support has been the frame-work upon which this program was built. We have microcomputers that are linked directly to microbiology, pharmacy, billing, and admissions, downloading data several times daily. An expert software system merges all of the data, and from this we can target patients for real-time interventions. The computer system allows all inpatients to be screened for either infection control or antibiotic management interventions on a daily basis, with minimal time being spent on data collection and maximal efforts devoted to interventions at the bedside. Additionally, the infection management program will assist in maintaining the extraordinarily low expenditures on antimicrobial agents. During 1993, the Millard Fillmore Health System spent $924,884 on antibiotics, an amount approximately 50% that of comparably sized hospitals.

Anti-Bacterial Agents↗
PubMed1997

In nosocomial pneumonia, optimizing antibiotics other than aminoglycosides is a more important determinant of successful clinical outcome, and a better means of avoiding resistance.

In in vitro and animal models, antibiotics show good relationships between concentration and response, when response is quantified as the rate of bacterial eradication. The strength of these in vitro relationships promises their utility for dosage regimen design and predictable cure of infections such as nosocomial pneumonia. In spite of their intuitive logic, close relationships between dosage and bacterial eradication have not been easy to show in clinical studies of nosocomial pneumonia. Presumably, a variety of patient, disease, bacterial, and pharmacokinetic variables cloud these relationships in patients, and delay their elucidation in patient trials. Patients with serious infections like nosocomial pneumonia require bactericidal antimicrobial activity. Studies in our laboratory show that the minimum effective antimicrobial action is an area under the inhibitory titer (AUIC) of 125, in which AUIC is calculated as the 24 hour serum area under the curve (AUC) divided by the minimum inhibitory concentration (MIC) of the pathogen. This target AUIC may be achieved with either a single antibiotic or it can be the sum of AUIC values of two or more antibiotics. There is considerable variability in the actual AUIC value for patients when antibiotics are administered in their usual recommended dosages. Examples of this variance will be provided using aminoglycosides, fluoroquinolones, and beta-lactams. The achievement of minimally effective antibiotic action, consisting of an AUIC of at least 125, is associated with bacterial eradication in about 7 days for beta-lactams and quinolones. Adding an aminoglycoside to beta-lactams may produce a slight increase in their rate of bacterial killing in vivo, but because of their narrow therapeutic window, and the associated low doses in relation to MIC, there are situations in which the aminoglycosides may be unable to add sufficient additional AUIC. Antibiotic activity indices allow clinicians to evaluate individualized patient regimens. Furthermore, antibiotic activity is a predictable clinical endpoint with predictable clinical outcome. This value also is highly predictive of the development of bacterial resistance. Antimicrobial regimens that do not achieve an AUIC of at least 125 cannot prevent the selective pressure that leads to overgrowth of resistant bacterial subpopulations. The methods based on the determination of AUIC have clinical applicability in routine practice, through software developed for this purpose. These indices can assist with patient management strategies in a prospective manner because they can identify patients at high risk of therapeutic failure or acquired resistance early in therapy before therapy fails. Our studies show that calculations of AUIC can be used to prospectively target regimens to improve the chances of cure with nosocomial pneumonia and other serious infections. A clinical intervention team has been organized to optimize antimicrobial regimens as early in therapy as possible, to lower the high cost events such as failure and acquired bacterial resistance.

Aminoglycosides↗
PubMed1991

Mathematical examination of dual individualization principles (I): Relationships between AUC above MIC and area under the inhibitory curve for cefmenoxime, ciprofloxacin, and tobramycin.

Traditional antibiotic dosage adjustments target predetermined serum concentrations, whereas a host of in vitro studies and recent clinical trials establish that bacteria vary in their susceptibility. Dual individualization, which considers the variance in both antibiotic pharmacokinetics and bacterial susceptibility, has been employed to describe different rates of bacterial eradication in relation to varying serum concentrations. In patients with nosocomial pneumonia, one of the model compounds studied was cefmenoxime, where a target six-hour area under the serum concentration-time curve (AUC) of 140 micrograms.h/mL above minimum inhibitory concentration (MIC) was previously associated with bacterial eradication in an average of four days. The target AUC value of 140 micrograms.h/mL above MIC is unique to cefmenoxime. Ideally, there should be a dual individualized target useful to adjust the dose of any antibiotic. Computer simulations performed to evaluate this hypothesis suggested that each antibiotic had a unique value for target AUC above MIC. These simulations indicated that an optimal AUC above MIC was about 80 percent of the total AUC above the MIC. Predictable rates of bacterial eradication would presumably result from maintaining these relationships across the range of bacterial susceptibility and the range of serum concentration profiles. Each antibiotic has a unique and different 24-hour AUC over MIC value associated with bacterial eradication in 4 days. For cefmenoxime, the target was 540 area units over MIC per 24 hours, tobramycin with 34 area units, and ciprofloxacin with 23 area units per 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefmenoxime↗
PubMed1989

Effects of enteral and intravenous antimicrobial treatment on survival following intestinal ischemia in rats.

One hundred and twenty rats underwent transection of the superior mesenteric artery. The animals were randomly divided into eight groups of 15 animals. Control group 1 and groups 3, 5, and 7 received intravenous normal saline, gentamicin, metronidazole, and gentamicin plus metronidazole, respectively. Control group 2 and groups 4, 6, and 8 received the same compounds enterally. Small and large bowel sections were taken postmortem and a necrosis score was assigned in blinded fashion. Gentamicin did not prolong survival, indicating that gram-negative microbes were not important in this pathology. Longer survival times for animals given either metronidazole or gentamicin plus metronidazole (P less than 0.01) indicate that anaerobes were a causative factor in mortality. During the first 15 hr after ischemia, antibiotics did not change mortality. After 15 hr, enteral administration was superior to intravenous administration in any regimen including metronidazole (P less than 0.01).

Animals↗
PubMed1988

Kinetics and action of N-methylthiotetrazole in volunteers and patients. Population-based clinical comparisons of antibiotics with and without this moiety.

Normal volunteers and patients were studied to determine the relative importance of NMTT and patient risk factors in the production of hypoprothrombinemia. The normal volunteers demonstrated in vivo NMTT production, but the order of magnitude (cefoperazone, moxalactam, and cefotetan in descending order) was different from the usual order of clinical risk. In patients, there was not a NMTT-concentration-versus-effect relationship. Patients who were vitamin K deficient were more sensitive to lower NMTT concentrations than those with normal vitamin K status. In surveillance studies, NMTT-containing antibiotics were nor more frequently associated with hypoprothrombinemia or bleeding than antibiotics that lack this moiety.

Azoles↗
PubMed1987

Determinants of antibiotic-associated hypoprothrombinemia.

Hypoprothrombinemia is a relatively uncommon event in the hospitalized patient. When it does occur, it often is associated with surgery, dietary vitamin K deficiency, renal dysfunction, malignancy, and broad-spectrum antibiotic therapy. Several mechanisms have been proposed to account for antibiotic-associated hypoprothrombinemia, including eradication of gastrointestinal bacteria, direct inhibition of vitamin K-dependent coagulation, and indirect inhibition of coagulation. The anecdotal reports and comparative studies of antibiotic-associated hypoprothrombinemia were reviewed; these usually implicated broad-spectrum or the use of several antibiotics. The increased frequency of hypoprothrombinemia associated with moxalactam and cefoperazone also raises questions about the role of their N-methylthiotetrazole (NMTT) side chains. The hypoprothrombinemia associated with NMTT antibiotics does not occur in healthy volunteers and is rare in patients without complicating conditions. Although NMTT inhibits vitamin K-dependent carboxylation in vitro, the parent cephalosporins do not. It is not clear whether NMTT-containing antibiotics liberate sufficient amounts of NMTT in vivo to antagonize clotting in patients. Thus, although moxalactam, and possibly cefoperazone, may in some cases be responsible for increases in prothrombin time, most important question for further study is whether the newer NMTT-containing antibiotics pose a risk of hypoprothrombinemia that is greater than that of antibiotics lacking this side chain.

Animals↗
PubMed1987

Single-dose accumulation pharmacokinetics of tobramycin and netilmicin in normal volunteers.

The two-compartment tissue accumulation pharmacokinetics of tobramycin and netilmicin were compared in 11 normal volunteers by using a crossover design. After each 1.0-mg/kg (body weight) dose, serum was collected for 96 h, and complete 24-h urine collections were obtained for a total of 30 days. Two months of washout were required before crossover. Concentrations in serum and urine were measured by radioimmunoassay, and concentrations in serum and urinary excretion rates were simultaneously fitted to a two-compartment pharmacokinetic model. Netilmicin exhibited significantly lower total body clearance (48 versus 90 ml/min) and longer terminal elimination half-life (161 versus 96 h) than tobramycin. As a result of these pharmacokinetic differences, the predicted tissue accumulation of netilmicin at steady state was significantly higher than that of tobramycin (P less than 0.05). Relative rates of aminoglycoside nephrotoxicity probably depend on both the differential tissue uptake (accumulation) and the concentration of the aminoglycoside which produces intracellular toxicity. Because the steady-state tissue accumulation of netilmicin is nearly 2.5 times greater than that of tobramycin, its potency in the production of intracellular toxicity needs to be that much less for the two agents to produce the same incidence of clinical nephrotoxicity.

Adult↗
PubMed1982

Renal handling of gentamicin by normal and ischemic canine kidneys.

The purpose of this study was to examine the pharmacokinetics of gentamicin renal uptake in dogs and assess the role of chronic renal ischemia. A stenosing silver clip was place on the left renal artery of four mongrel dogs. Six months later, each dog received an infusion of gentamicin and inulin. Blood and urine samples were collected serially. In each dog, the ischemic left kidney was smaller and had a lower RPF and CCR. The decrease in CCR was highly correlated with the decrease in RPF. Measured gentamicin kidney concentrations were found to be in good agreement with predicted values based on the amount reabsorbed and the kidney weight. Within each animal (control vs. ischemic kidney), there was a significant correlation between the filtered load of gentamicin and both the renal reabsorption and excretion of gentamicin. These relationships exhibited high R2 values, demonstrating that the induced ischemia did not alter the filtration or reabsorbtive mechanisms of gentamicin within the animal, but only decreased the filtered load. Between animals, gentamicin excretion was proportional to filtered load, but gentamicin reabsorption had the lowest r2 value, explaining only 49% of the observed variance. The unexplained variance encountered in gentamicin reabsorption between animals establishes that there are important determinants of renal tissue concentration that are independent of filtration or filtered load. This study suggests that a reduction in glomerular filtration is not an important risk factor for elevated gentamicin renal tissue concentrations, provided that serum concentrations are controlled within the therapeutic range.

Absorption↗
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

A microcomputer program for tobramycin consult services, based on the two-compartment pharmacokinetic model.

A microcomputer program has been developed to provide assistance to tobramycin clinical pharmacokinetic consult services. Written for the Apple II Plus computer with 64 K memory, one-disk drive, and a dot matrix graphics printer, this software is user-oriented and simple to operate. The program disk contains complete documentation and referenced instructions. Major sections provide empiric dosing recommendations based on population data and allow determination of dosage from measured serum concentrations. The program keeps a record of previous regimens, allows for the entry of the user's own recommendation, and provides complete flexibility for up to 15 dosage and interval changes. In addition to its dosing information and file management capabilities, the program simulates serum concentration profiles based on user-selected one-compartment, two-compartment, or two-compartment prenephrotoxic models. The program prints a consult sheet with concentration vs. time simulation, patient demographic data, and user-entered recommendations and comments. The program provides extensive disk storage capabilities for patient files, with immediate access to facilitate updating and dosing regimen changes as they occur. In addition to providing improvements in empiric dosing capabilities, pharmacokinetic modeling, and data handling, this computer software has been designed to incorporate pharmacokinetic data derived from important subpopulations into the empiric dosing algorithms. This unique aspect enables the program to provide improved empiric dosing regimens for patients who do not fall under the guidelines for any of the conventional aminoglycoside dosing nomograms.

Aging↗