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Biomedical subjects

S H Zinner

Publications and source records attributed to S H Zinner.

At least 19 recordsLinked to original sources
PubMed1992

Management of urinary tract infections in pregnancy: a review with comments on single dose therapy.

Most investigators agree that the adverse effects of urinary tract infections in pregnancy can be abrogated by effective early detection and treatment. However, the optimal methods for screening and treatment remain controversial. Although single-dose therapy has not been applied to pregnant women with acute pyelonephritis, most but not all studies which have compared single-dose with longer courses of beta-lactam or other antibiotics in pregnant asymptomatic bacteriuric women have shown no differences in outcome. This paper reviews recent trials of single-dose treatment of bacteriuria in pregnant women.

Anti-Infective Agents, Urinary↗
PubMed1991

Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection.

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.

Azlocillin↗
PubMed1991

Single daily dosing of amikacin in an in-vitro model.

The pharmacodynamics of amikacin given as a single daily dose was compared with standard divided dosing in an in-vitro model of infection. This model allows the exposure of log phase bacteria to changing concentrations of antibiotics that simulate the kinetics of the drugs in human patients. Two strains of Pseudomonas aeruginosa, one sensitive and one resistant to azlocillin were studied (MICs for amikacin were 16 and 8 mg/l respectively). Simulated drug regimens included: amikacin 400 mg q 8 h; amikacin 1.2 g q 24 h; and azlocillin 4 g q 12 h. Each regimen alone and both combinations of amikacin plus azlocillin were studied. With both amikacin regimens initial rapid killing was followed by regrowth of resistant subpopulations. Azlocillin alone produced minimal killing of the resistant strain and moderate killing with ultimate bacteriostasis of the susceptible strain. Bacterial regrowth was prevented with both combination regimens with the single daily dose of amikacin plus azlocillin producing the most rapid and complete killing, especially of the azlocillin resistant strain. These data support further clinical studies of single daily dosing of aminoglycosides.

Amikacin↗
PubMed1991

Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group.

Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients.

Adult↗
PubMed1991

Maternal prenatal dietary potassium, calcium, magnesium, and infant blood pressure.

We studied the association between the prenatal diets of 212 mothers assessed by a semiquantitative food frequency questionnaire and the blood pressure of their infants. Prenatal potassium, calcium, and magnesium intakes were measured and adjusted for total caloric intake. Infant blood pressure was measured at 2-3 days and at 1, 6, and 12 months of age by using an ultrasonic-auscultatory device and was adjusted for cuff size, observer, and sleep/activity status, age in days in neonates, and weight at 6 and 12 months. Maternal prenatal potassium intake was inversely related to diastolic pressure at 6 months (r = -0.28, p less than 0.01) and at 12 months (r = -0.30, p less than 0.05). After adjustment for neonatal breast versus formula feeding, maternal prenatal calcium intake was inversely related to systolic blood pressure at 1 month (r = -0.21, p less than 0.01), and to diastolic blood pressure at 6 months (r = -0.27, p less than 0.01) and 12 months (r = -0.24, p less than 0.05). Maternal prenatal magnesium intake was inversely related to 6-month systolic blood pressure (r = -0.20, p less than 0.05). In multivariable models with all three cations, maternal prenatal potassium intake was independently and inversely related to diastolic blood pressure at 6 and 12 months. Maternal prenatal calcium intake was independently related to 1-month systolic and 6-month diastolic blood pressure. Age-specific infant blood pressure differences between the upper and lower quartiles of maternal prenatal cation intakes ranged from 3 to 7 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

Sexual behavior of college women in 1975, 1986, and 1989.

To compare sexual practices in college women before and after the start of the current epidemics of Chlamydia trachomatis, genital herpesvirus, and human immunodeficiency virus type 1 infection, we surveyed 486 college women who consulted gynecologists at a student health service in 1975, 161 in 1986, and 132 in 1989 at the same university. There were no statistically significant differences in age, age at menarche, or reason for visiting the gynecologist. The percentages of women in this population who were sexually experienced were the same in all three years (88 percent in 1975, 87 percent in 1986, and 87 percent in 1989). Oral contraceptives were used by 55 percent of the women in 1975, 34 percent in 1986, and 42 percent in 1989; the use of condoms as the usual method of birth control increased (6 percent in 1975, 14 percent in 1986, and 25 percent in 1989; P less than 0.001). In 1975, only 12 percent reported the regular use of condoms during sexual intercourse, in some cases in conjunction with other methods of contraception, as compared with 21 percent in 1986 and 41 percent in 1989 (P = 0.0014). No significant differences were found in the three surveys in the number of male sexual partners or the frequency of fellatio, cunnilingus, or anal intercourse. An additional sample of 189 college women who did not consult the health service was surveyed in 1989, and similar sexual behavior was reported by those who were sexually experienced (65 percent). We conclude that in this population there has been little change in sexual practices in response to new and serious epidemics of sexually transmitted diseases, with the exception of an increase in the use of condoms (which still does not reach 50 percent).

Adolescent↗
PubMed1990

Significance of "extravascular" protein binding for antimicrobial pharmacodynamics in an in vitro capillary model of infection.

The effect of protein binding in an "extravascular" space on antimicrobial pharmacodynamics was studied in an in vitro capillary model of infection. Simulated 500-mg oral doses of dicloxacillin (approximately 96% bound) or cephalexin (less than 5% bound) were administered every 6 h for four doses. A 10-fold-higher dose of dicloxacillin was also studied to determine the effect of drug concentration on the reduction of bacterial killing in the presence of protein. Staphylococcus aureus ATCC 25923 was inoculated into peripheral chambers filled with either Mueller-Hinton broth or Mueller-Hinton broth plus 25% human serum. Serial samples for bacterial counts were collected over 24 h. The presence of serum in the chambers significantly reduced bacterial killing by dicloxacillin but not by cephalexin during the first 6 h (two-way analysis of variance, F = 6.04, P less than 0.05) but not at 24 h. Reduction of dicloxacillin activity in serum-containing chambers persisted with the higher dose. These data suggest that despite attaining higher total drug concentrations in protein-containing extravascular spaces with highly bound drugs, protein binding reduces bactericidal activity during the early stages of treatment in this model.

Anti-Infective Agents↗
PubMed1990

Pharmacokinetics and bioavailability of intravenous-to-oral enoxacin in elderly patients with complicated urinary tract infections.

The pharmacokinetics of oral fluoroquinolone antibiotics in normal volunteers have been studied extensively; however, limited patient data exist. Enoxacin steady-state pharmacokinetics and bioavailability were determined following repeated 400-mg intravenous (i.v.) and oral dosing by using compartmental and noncompartmental methods in 10 elderly (mean age, 73.8 years) men with complicated urinary tract infections. Average peak enoxacin concentrations following i.v. and oral dosing were 8.15 and 5.45 mg/liter, respectively. Mean values for major pharmacokinetic parameters (noncompartmental) were similar following i.v. and oral administration, respectively: area under the concentration-time curve from 0 to 12 h, 47.6 and 41.0 mg.h/liter; volume of distribution or volume of distribution/bioavailability, 1.61 and 1.99 liters/kg; total body clearance or total body clearance/bioavailability, 2.58 and 3.01 ml/min per kg; and half-life, 8.2 and 9.1 h. Parameters from analysis of enoxacin plasma concentration data by using a two-compartment pharmacokinetic model also revealed marked similarities between the two administration routes. Enoxacin was highly bioavailable (mean, 86.97%) following oral administration.

Administration, Oral↗
PubMed1990

The prevalence of dyspareunia.

A questionnaire regarding sexual experience and dyspareunia was sent to 428 women, of whom 324 (75.7%) responded. Ten refused to participate and one had never had heterosexual intercourse, leaving 313 evaluable responders. One hundred twenty-two (39.0%) had never had dyspareunia and 86 (27.5%) had had dyspareunia at some point in their lives which resolved, either spontaneously or with specific treatment. One hundred five women (33.5%) still had dyspareunia at the time of the survey, 51 of whom had had dyspareunia for their entire active sexual lives. Twenty-two (21%) rarely had dyspareunia, 58 (55.2%) occasionally had discomfort, and 25 (23.8%) had dyspareunia frequently or virtually all the time. Frequency of intercourse was not different among any of the groups analyzed, although 49 (48.0%) of the women reported a decrease in sexual frequency and 35 (33.7%) reported an important adverse effect on their relationships as a result of dyspareunia. Most of the women had not discussed their dyspareunia with a health care professional and were unaware of the cause of their problem.

Coitus↗
PubMed1989

Serum inhibitory and bactericidal activity of ciprofloxacin following intravenous administration.

Serum inhibitory and bactericidal titers were measured in nine healthy volunteers following single iv doses of ciprofloxacin 100, 150, and 200 mg. The median peak serum bactericidal titer (5 minutes following completion of a 30-minute infusion) against two highly susceptible strains of Escherichia coli ranged between 1:64 and 1:1024 and titers exceeded 1:8 for six hours for all dose levels. The bactericidal titers against two strains of Pseudomonas aeruginosa and a methicillin-resistant strain of Staphylococcus aureus were considerably lower, the median peak being 1:2 at all dose levels. Measured inhibitory and bactericidal titers at five minutes and one hour postinfusion were significantly greater than those predicted (measured serum ciprofloxacin concentration to minimum inhibitory concentration [MIC] or minimum bactericidal concentration [MBC]) for only one strain of E. coli. Intravenous doses of ciprofloxacin 100-200 mg produce high and sustained serum bactericidal titers against highly susceptible bacteria; considerably lower levels of activity are seen against bacteria having higher MICs and MBCs but still considered susceptible to the drug.

Adult↗
PubMed1989

Clinical overview of enoxacin.

Enoxacin is a new fluoroquinolone that will be available as oral and intravenous preparations. This drug is bactericidal for a wide range of organisms, including Staphylococcus aureus, S. epidermidis, Enterobacteriaceae and Pseudomonas aeruginosa. In addition, Neisseria gonorrhoeae is exquisitely susceptible, as is Branhamella catarrhalis. The evaluation of the clinical activity of enoxacin is still relatively new, but published studies reveal a good deal of potential in the treatment of infections caused by susceptible bacteria in the urinary tract, upper and lower respiratory tracts, bones and joints, and the gastrointestinal tract. The general use of this drug has been associated with few adverse reactions. Further published data, as well as the results of comparative trials now in progress, will permit a thorough clinical evaluation of this useful drug.

Bacterial Infections↗
PubMed1988

Effect of dose and schedule on cefoperazone pharmacodynamics in an in vitro model of infection in a neutropenic host.

Previous studies have shown that cefoperazone given in frequent, large doses is effective in the treatment of infection in patients with cancer. The pharmacodynamics of 2- and 4-g doses of cefoperazone administered either as a single dose or at 12-hour intervals were studied in an in vitro model that simulates infection in a neutropenic patient. One strain each of Pseudomonas aeruginosa (minimal inhibitory concentration [MIC] = 2 micrograms/ml), Staphylococcus aureus (MIC = 1 microgram/ml), Escherichia coli (MIC = 0.06 micrograms/ml), and Klebsiella pneumoniae (MIC = 0.25 micrograms/ml) was studied. The initial dose reduced the inoculum by approximately 3 logs for the Pseudomonas and the staphylococci and 3 to 5 logs for the other organisms. No significant differences in killing were found between the 2- and 4-g doses. Regrowth of Pseudomonas and staphylococci occurred with the single dose but not with the every-12-hour regimen. These data support the clinical use of cefoperazone in doses every 12 hours.

Agranulocytosis↗
PubMed1988

Symptoms associated with vaginal colonization with yeast.

We correlated vulvovaginal symptoms with vaginal cultures for yeast in healthy female college students. Yeasts were isolated from 42 (29.2%) of 144 women. Only four (22%) of 18 women with positive fungal cultures had fungal elements visualized microscopically in vaginal material suspended in 10% potassium hydroxide (potassium hydroxide wet preparations). Symptoms, mainly vulvovaginal itching and irritation, were reported by 28 (67%) of 42 women whose cultures contained yeast and by 22 (22%) of 102 women who were not colonized by yeast (p less than 0.01). We conclude that vaginal colonization by yeasts is commonly associated with vulvovaginal symptoms, often in the absence of positive potassium hydroxide wet preparation results. These data suggest that vaginal specimens from women who have vulvovaginal symptoms and negative potassium hydroxide wet preparation results should be cultured for fungi before the diagnosis of fungal vulvovaginitis is excluded.

Adolescent↗
PubMed1988

Empiric antimicrobial therapy for febrile granulocytopenic cancer patients: lessons from four EORTC trials.

The results of the four EORTC trials conducted over the past 15 years suggest: (1) early empiric therapy with broad spectrum antibiotics directed against gram-negative bacterial bacteremia (GNBB) is a reasonable approach in febrile granulocytopenic patients (GCP); (2) the level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; severely and/or persistently neutropenic patients are the true tests of antibiotic efficacy and they benefit from antimicrobial synergism; (3) mortality from GNBB in GCP is not related directly to a given empiric antimicrobial regimen which may 'buy time' and allow appropriate therapeutic alterations; (4) only microbiologically documented infections and especially bacteremias are useful to compare responses to antimicrobial regimens; (5) the response rate of GNBB is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen and emergence of resistance to some antibiotics (cephalothin, carbenicillin, ticarcillin, azlocillin) has rendered some combinations less effective. The combination of an anti-Pseudomonas beta-lactam plus an aminoglycoside is recommended as the 'standard' for empiric therapy in febrile GCP; (6) gram-positive pathogens have become a common cause of bacteremia in GCP and although the response rate to empiric regimens may be marginal, the associated mortality is low. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.

Agranulocytosis↗
PubMed1987

Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia.

To determine whether combination antibiotic therapy including a short course of an aminoglycoside was as effective and less toxic than a conventional long course of the combination for the empirical therapy of gram-negative bacteremia in patients with cancer and granulocytopenia, we conducted a randomized multicenter trial comparing ceftazidime plus a short course (three days) of amikacin, ceftazidime plus a long course (nine days) of amikacin, and azlocillin plus a long course (nine days) of amikacin. Single-organism gram-negative bacteremia occurred in 129 of 872 evaluable patients. Without a change in antibiotics, the response rates were 81 percent with ceftazidime and long-course amikacin, 48 percent with ceftazidime and short-course amikacin (P = 0.002), and 40 percent with azlocillin and long-course amikacin (P less than 0.001). Among patients with fewer than 100 granulocytes per cubic millimeter throughout therapy, the response rates were 6 percent with ceftazidime and short-course amikacin and 50 percent with ceftazidime and long-course amikacin (P = 0.03). Linear logistic-regression analysis showed that therapy with ceftazidime and long-course amikacin was the most favorable prognostic factor of the response to infection, whereas the presence of leukemia or shock was the least favorable. We conclude that ceftazidime should be given in combination with a conventional full course of an aminoglycoside (amikacin) when used for the empirical treatment of gram-negative bacteremia in cancer patients with granulocytopenia.

Adolescent↗
PubMed1987

Pharmacokinetics and pharmacodynamics of intravenous ciprofloxacin. Studies in vivo and in an in vitro dynamic model.

The pharmacokinetics and pharmacodynamics of a 200-mg intravenous dose of ciprofloxacin were studied in normal volunteers and in an in vitro dynamic model that exposes bacteria to changing concentrations of the drug in a neutropenic setting. Peak ciprofloxacin concentrations in vivo averaged 3.2 micrograms/ml. The terminal serum elimination half-life averaged 4.2 hours. The volume of distribution of ciprofloxacin was large and consistent with extensive extravascular distribution. Slightly less than half of the dose was recovered unchanged in urine by 48 hours after infusion. The median serum bactericidal titer against a strain of Escherichia coli was 1:16 or more for at least six hours after infusion, but was only 1:2 against a strain of Pseudomonas aeruginosa immediately after the end of the infusion. Pharmacodynamic studies in the in vitro model with a simulated regimen of 200 mg administered intravenously every 12 hours demonstrated rapid and complete killing of this strain of E. coli following the first 200-mg "dose." For the strain of P. aeruginosa, an initial bactericidal effect was observed due to the eradication of susceptible subpopulations of bacteria; however, regrowth of resistant organisms was observed. These data suggest that a regimen of 200 mg administered intravenously every 12 hours results in rapid killing of susceptible bacteria. Higher doses or combination therapy may be required to prevent the emergence of resistant P. aeruginosa in this model and in the setting of neutropenia.

Bacterial Infections↗