Biomedical subjects
Publications and source records attributed to L M Albrecht.
Many of the above references will provide the necessary information to determine the safety of drugs during breastfeeding. Because interpretation of existing data varies in these references, it is prudent to consult with more than one resource. References should be routinely updated every 1 to 2 years as new drugs and literature are made available.
Women who suffer from postpartum depression require treatment. Caution must be exercised if any antidepressant is used. These agents concentrate in the central nervous system; therefore, serum concentrations and breastmilk: plasma ratios may not accurately predict infant drug exposure. Since there is no absolute contraindication to breastfeeding during antidepressant use, recommendations should be made on a case-by-case basis limited to healthy term infants. When possible plasma antidepressant concentrations, including metabolites, should be measured in the infant. Frequent developmental follow-up, not only during the treatment period but throughout childhood, should be performed on these infants.
The pharmacokinetics of teicoplanin were determined after multiple 30-min intravenous infusions of 10 to 15 mg/kg every 12 to 24 h in 11 intravenous drug abuse (IVDA) patients being treated for bacterial endocarditis. Multiple serum samples were obtained over 7 to 14 days. Twenty-four-hour urine collections were obtained on days 1 and 5. Serum concentration-time data were analyzed by using multiple-dose pharmacokinetic analysis (NONLIN84). Results were compared with pharmacokinetic parameters derived from previous studies in normal healthy volunteers following multiple intravenous infusions of teicoplanin (3 to 6 mg/kg/day). Total and renal clearances of teicoplanin in IVDA patients were found to be significantly greater and more highly variable than those observed previously in normal healthy volunteers. As a result, predicted steady-state trough concentrations in serum may vary up to fivefold. The mechanism responsible for this variation appears to be related to the glomerular filtration rate. In IVDA patients, individualized teicoplanin dosage may be required in the treatment of bacterial endocarditis.
The efficacy of fleroxacin was compared with that of vancomycin by using the rabbit model of methicillin-susceptible Staphylococcus aureus endocarditis. Animals received intravenous therapy with fleroxacin, 30 mg/kg every 8 h, or vancomycin, 17.5 mg/kg every 6 h, for 4 days. Both antimicrobial agents effectively cleared bacteremia and significantly reduced bacterial counts in vegetations and tissues compared with those in untreated controls. However, resistance to fleroxacin at 5- and 10-fold the MIC arose in the test strain of S. aureus in 73 and 27%, respectively, of animals that received the drug. Resistant isolates were found mainly in vegetations and were composed of up to 7% of the residual population recovered from that site. We conclude that fleroxacin is as effective as vancomycin in this model of a serious systemic S. aureus infection, but resistance to the drug may develop during therapy. If similar results are found with other strains of S. aureus during therapy with this or other fluoroquinolones, such data, when they are combined with the high incidence of fluoroquinolone resistance among S. aureus isolates being reported from selected institutions, would support the contention that these drugs should not be used as first-line therapeutic agents for S. aureus infections.
The incidence of nephrotoxicity in patients receiving vancomycin alone or in combination with an aminoglycoside was prospectively evaluated. A total of 231 courses of antibiotic therapy in 224 patients were consecutively monitored over 28-month period. One hundred and sixty-eight patients received vancomycin alone, 63 patients received vancomycin with an aminoglycoside, and 103 patients received gentamicin. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a 50% increase above baseline, whichever was greater. Eight patients (5%) receiving vancomycin alone, 14 patients (22%) receiving vancomycin with an aminoglycoside, and 11 patients (11%) receiving gentamicin alone were found to have nephrotoxicity. Factors found to be associated with increased risk of nephrotoxicity in patients receiving vancomycin were concurrent therapy with an aminoglycoside, length of treatment with vancomycin (greater than 21 days), and vancomycin trough serum concentration (greater than 10 mg/l). Although the incidence of vancomycin nephrotoxicity is low, patients receiving vancomycin therapy with the above risk factors should be closely monitored.
The efficacy of ofloxacin was compared with that of vancomycin in the therapy of experimental Staphylococcus aureus endocarditis. Rabbits infected with either a methicillin-susceptible (MSSA-1199) or a methicillin-resistant (MRSA-494) test strain were treated with ofloxacin (20 mg/kg of body weight every 8 h) or vancomycin (17.5 mg/kg of body weight every 6 h) for 4 days. The antimicrobial agents were found to be equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and in renal and splenic tissue of animals infected with either test strain. The drugs were of equal efficacy in curing MRSA-494 endocarditis. No resistance to ofloxacin emerged in either test strain during therapy. We conclude that in this model ofloxacin is as efficacious as vancomycin and that, unlike for other fluoroquinolones we have evaluated, resistance to the drug does not develop during therapy of this serious S. aureus infection.
The pharmacokinetics of vancomycin were evaluated in 34 patients (10 burn patients, 14 intravenous drug abusers [IVDA], and 10 controls). Multiple serum samples were drawn following a 1-h vancomycin infusion at steady state over an 8- to 12-h dosing interval. Pharmacokinetic parameters were derived by noncompartmental analysis. There were no significant differences among the groups with respect to age, weight, serum creatinine, volume of distribution, or protein binding. Burn patients had a significantly higher creatinine clearance than did IVDA or controls. Vancomycin clearances averaged 142.8, 98.0, and 67.7 ml/min in burn patients, IVDA, and controls, respectively. The renal clearance of vancomycin was also higher in burn patients than in the other groups. IVDA tended to have a higher vancomycin clearance (31% higher) than did controls, but the difference was not statistically significant. Vancomycin clearance was much higher in burn patients requiring dosage individualization and close monitoring. A considerable amount of vancomycin was eliminated through renal tubular secretion, making dosage predictions based on creatinine clearance more difficult. Further work with IVDA will be needed to determine if they represent a group requiring aggressive vancomycin dosages.
The efficacy of fleroxacin versus that of vancomycin was assessed by using the rabbit model of methicillin-resistant Staphylococcus aureus endocarditis. Animals were treated with fleroxacin (30 mg/kg of body weight every 8 h) or vancomycin (17.5 mg/kg every 6 h) for 4 days. These antimicrobial agents were equally effective in clearing bacteremia, reducing bacterial counts in vegetations and tissues, and curing endocarditis. However, resistance to fleroxacin at fivefold the MIC arose in the test strain of S. aureus in 8% of animals that received the drug. We conclude that fleroxacin is as efficacious as vancomycin in this model of a serious systemic S. aureus infection, but modest resistance to fleroxacin may develop during therapy.
The therapeutic activities of ciprofloxacin (25 mg/kg every 8 h), rifampin (10 mg/kg every 24 h), ciprofloxacin plus rifampin, and vancomycin (17.5 mg/kg every 6 h) were compared by using the rabbit model of Staphylococcus aureus endocarditis. Animals infected with one of two test strains (SA1199 or SA487) were randomized into treatment groups and received 6 days of therapy. For SA1199, ciprofloxacin plus rifampin was most effective at reducing vegetation bacterial counts. For SA487, ciprofloxacin plus rifampin was as effective as vancomycin but less effective than ciprofloxacin alone. Resistance to ciprofloxacin at 5- and 10-fold the MIC emerged in the test strain in 82 and 55%, respectively, of rabbits infected with SA1199 and receiving ciprofloxacin monotherapy. The combination of ciprofloxacin and rifampin decreased these frequencies to 60% (P = 0.27) and 10% (P = 0.04). No resistance to ciprofloxacin was found in rabbits infected with SA487. We conclude that ciprofloxacin and ciprofloxacin plus rifampin are as efficacious as vancomycin in this model and that combining rifampin with ciprofloxacin may decrease the frequency at which high-level resistance to ciprofloxacin emerges. However, with respect to improved efficacy, the combination of ciprofloxacin and rifampin is unpredictable and may be detrimental.
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.
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.
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Enoxacin, a new broad spectrum azaquinolone, has demonstrated in-vitro activity against Neisseria gonorrhoeae including penicillinase producing strains. We evaluated the safety and efficacy or oral enoxacin 400 mg versus intramuscular ceftriaxone 250 mg for the treatment of uncomplicated genital N. gonorrhoeae infections. Of the 57 patients enrolled, 48 patients (26 men, 22 women) were culture positive and returned for the follow up visit. Six patients (12.5%) had penicillinase producing strains of N. gonorrhoeae, and eleven patients (23%) had concomitant Chlamydia trachomatis infections. Genital gonorrhea was eradicated in 98% of the patients, with a cure rate of 22/23 (96%) in the enoxacin group and 25/25 (100%) in the ceftriaxone group. There were no consequential side effects noted for either agent. Oral enoxacin is a safe and efficacious alternative for the treatment of uncomplicated N. gonorrhoeae infections.
Coagulase-negative staphylococci (CNS), which historically have been viewed as contaminants when recovered in culture media, are now recognized as opportunistic pathogens of increasing importance in hospital-acquired infections. They are frequently found colonizing prosthetic devices and intravenous lines. CNS are capable of producing a variety of infections including deep-seated infections such as endocarditis and meningitis. Staphylococcus epidermidis is the most commonly isolated CNS and it appears to be the most resistant to antibiotics, making antimicrobial therapy challenging. Treatment of the infection will very often require removal of a prosthetic device, if present. An adequate infection control program is imperative in prophylaxis against this infection.
The protein binding of vancomycin has been reported to range from less than 10 percent to 82 percent. We examined the binding of vancomycin in 34 patients (14 intravenous drug abusers, 10 burn patients, and 10 control patients) with Staphylococcus aureus infections. Blood samples were collected serially over an 8- or 12-hour dosing interval following a one-hour infusion. In vitro studies were also performed using albumin solutions of varying concentrations. Binding characteristics were determined through ultrafiltration with vancomycin concentrations analyzed for fluorescence polarization immunoassay. The unbound fraction of vancomycin ranged from 0.41 to 0.77 with a mean of 0.54 +/- 0.08. Unbound fractions was significantly correlated with serum albumin concentration (r = -0.344, p less than 0.046) and renal clearance (r = 0.394, p less than 0.021) but not with total body clearance or volume of distribution. In vitro data also showed an association between albumin concentration and unbound fraction (r = -0.94, p less than 0.017). Although vancomycin protein binding changes with serum albumin, this finding may have limited clinical significance.