Significant Difference In Clinical Response Research Articles

Outpatient treatment of acute pyelonephritis in pregnancy after 24 weeks

Objective: To compare outpatient to inpatient management of acute pyelonephritis in pregnancy beyond 24 weeks’ gestation. Methods: Ninety-two gravidas past 24 weeks’ gestation, randomized to outpatient or inpatient therapy, received two 1-g doses of intramuscular ceftriaxone at 24-hour intervals while hospitalized, then were discharged and reevaluated within 48–72 hours or remained hospitalized until afebrile for 48 hours. Subjects received oral cephalexin after initial treatment. Urine cultures were done on admission and 5–14 days after therapy. Surveillance continued until delivery. We anticipated that 15% of outpatients and 0.01% of inpatients would require changes in antibiotic therapy. Results: Twenty-one percent of women evaluated were excluded. Thirteen of 46 (28%) outpatients’ hospitalization exceeded 24 hours. Six outpatients (13.0%) and one inpatient did not respond to initial therapy and were treatment failures (relative risk [RR] 1.82, 95% confidence interval [CI] 1.00, 3.31). Within 2 weeks of initial therapy, seven of 81 (8.6%) subjects had positive urine cultures, four outpatients versus three inpatients ( P > .999). Eleven of 84 (13.1%) deliveries for which birth data were available occurred preterm (six of 41 outpatients versus five of 43 inpatients) (RR 1.14, 95% CI 0.61, 2.11). Conclusion: There were no significant differences in clinical responses or birth outcomes of inpatients or outpatients treated for acute pyelonephritis after 24 weeks’ gestation if they completed their assigned protocols. Thirty percent of outpatients were unable to, and most women with acute pyelonephritis in the third trimester were not candidates for outpatient therapy.

A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy

Objective: To compare the effectiveness of three antibiotic regimens for the treatment of acute pyelonephritis in pregnancy. Methods: One hundred seventy-nine pregnant women earlier than 24 weeks’ gestation who had acute pyelonephritis were randomized to 1) intravenous (IV) ampicillin and gentamicin, 2) IV cefazolin, or 3) intramuscular ceftriaxone. All participants then completed 10-day courses of oral cephalexin after primary treatment. A urine culture was performed on admission and 5–14 days after completion of therapy. Surveillance for persistent or recurrent infection and obstetric complications continued until delivery. On the basis of a two-sided hypothesis test and with α = .025, 60 subjects were needed in each group for statistical power greater than 80% to detect a difference between ceftriaxone and other antibiotics if hospital length of stay differed by 1 or more days. Results: The treatment groups were similar in age, parity, temperature, gestational age, and initial white blood cell count. There were no statistically significant differences in length of hospitalization, hours until becoming afebrile, days until resolution of costovertebral angle tenderness, or infecting organism. There were no statistically significant differences in birth outcomes between the three groups. The average (standard deviation) age at delivery was 38.8 ± 3.6 weeks. The average birth weight was 3274 ± 523 g. Eleven (6.9%) of 159 subjects delivered prematurely. Escherichia coli was the most common uropathogen isolated (137 of 179, 76.5%). Blood cultures were positive for organisms in 15 cases (8.4%). At follow-up examination within 2 weeks of initial therapy, eight (5.0%) of 159 subjects had urine cultures positive for organisms. Ten women (6.3%) had cultures positive for organisms later in their antepartum course, and 10 other participants (6.3%) developed recurrent pyelonephritis. Conclusion: There are no significant differences in clinical response to antimicrobial therapy or birth outcomes among subjects treated with ampicillin and gentamicin, cefazolin, or ceftriaxone for acute pyelonephritis in pregnancy before 24 weeks’ gestation.

Meta-analysis of the clinical outcome of carbapenem monotherapy in the adjunctive treatment of intra-abdominal infections

Background The carbapenems, a class of β-lactam antimicrobials with efficacy against both aerobic and anaerobic organisms, have demonstrated potential as monotherapeutic regimens in the treatment of serious intra-abdominal infections. Clinical trials have been conducted in the past decade to compare carbapenem monotherapy versus combinations of antibiotic therapy. We report here a meta-analysis of 10 such trials. Data sources An 11-year Medline search (from 1985 through 1996) of the English-language literature identified clinical trials that compared the outcomes of carbapenem monotherapy, either imipenem/cilastatin or meropenem, versus another antibiotic regimen in intra-abdominal infections in human subjects. Ten randomized, prospective trials were found, with a total of 1,227 clinically evaluable patients. A meta-analysis of these clinical trials was performed to determine the difference in clinical outcomes between carbapenem monotherapy versus other antibiotic regimens. We found a difference in response rates of −1.6% (95% confidence interval [CIJ −5.7% to 2.5%) and a response ratio of 0.99 (95% CI, 0.90 to 1.09), indicating no statistical significant difference. Conclusions A meta-analysis of 10 clinical trials from 1985 through 1996 has revealed no statistical significant difference in clinical response between carbapenem monotherapy and combinations of antibiotic therapy in intra-abdominal infections. We noted, however, that the earlier studies reported more favorable response ratios for carbapenems than later publications. This may have been due to the selection of less effective comparators in earlier studies. We conclude that carbapenem monotherapy is as effective as combinations of antimicrobials for the treatment of intra-abdominal infections.

A double-blind comparison of acitretin and etretinate in combination with bath PUVA in the treatment of extensive psoriasis

Thirty-four patients with extensive psoriasis were treated in a double-blind parallel fashion with either acitretin plus bath PUVA (trimethylpsoralen bath + UVA) or etretinate plus bath PUVA. Each group consisted of 17 patients. The dose of retinoid was 40 mg/day during the 2-week monotherapy phase and subsequently 20 mg/day during the combination treatment. Bath PUVA was given three times a week starting with a UVA dose of 0.06 J/cm2. Remission (greater than 90% improvement) was achieved in all patients in 6-10 weeks. There were no significant differences in clinical response between the two groups; the mean +/- SD PASI score (psoriasis area and severity index) before treatment was 22.6 +/- 7.1 in the acitretin-PUVA group and 19.4 +/- 7.8 in the etretinate-PUVA group. The corresponding figures after treatment were 0.6 +/- 0.6 and 1.0 +/- 0.5, respectively. Side-effects related to retinoid treatment were frequent in both groups but they were usually mild and well-tolerated. There was only one case of diffuse alopecia after 8 weeks in the etretinate-PUVA group. Scaling of the palms and soles was seen in six patients in the acitretin-group but only in two patients in the etretinate-group. Triglycerides were elevated in about half of the patients in both groups. The present study shows that acitretin is as effective as etretinate in the combination with bath PUVA.

Clindamycin Versus Chloramphenicol in Treatment of Anaerobic Infections: A Prospective, Randomized, Double-Blind Study

Seventy patients with substantiated anaerobic infections were treated parenterally with clindamycin or chloramphenicol in a prospective, double-blind, randomized study. No significant differences in clinical response or toxicity were noted between the two groups of patients.

CEFTRIAXONE VERSUS AMPICILLIN AND CHLORAMPHENICOL FOR TREATMENT OF BACTERIAL MENINGITIS IN CHILDREN

78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log 10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p<0·05).

Flupenthixol in depression: A study of serum levels and prolactin response

The relationship between improvement in symptomatology and changes in prolactin and serum cis-flupenthixol levels has been evaluated in 16 patients with a clinical diagnosis of depression, who were treated with 1 or 2 mg of flupenthixol in a once daily morning dose. No significant differences in clinical response were noted between those on 1 and 2 mg, and side effects were few. The presentation of some side effects, in particular extrapyramidal symptoms, were related to higher serum levels and prolactin levels particularly in the early stages of the study. Improvements in depressive symptoms were unrelated to serum levels, but at day 56 of the trial were positively correlated to changes in prolactin levels. Improvements in anxiety symptoms were positively related to serum levels at day 3 but negatively related at day 56. These results are discussed in the light of possible influences of dopamine antagonism in relation to an antidepressant effect.

Antihypertensive Effect of Oxprenolol and Chlorthalidone in Fixed Combination, Given Once Daily

In a multicentre, single-blind, within-patient study, the effectiveness and tolerability of the fixed combination oxprenolol 80 mg + chlorthalidone 10 mg per tablet given once daily, compared to the well established b.i.d. schedule, has been investigated in forty out-patients with mild to moderate hypertension. After a two-weeks placebo wash-out, twenty patients were given 1 tablet b.i.d. of the fixed combination for 4 weeks and thereafter 2 tablets once-daily for a further 4 weeks; the remaining twenty patients were given the fixed combination in the reverse order. There was no significant difference in clinical response between the two treatment regimes, which were equally effective and well tolerated. However, patient compliance might be considerably improved with the once-daily dosage schedule of the fixed combination.

Comparison of a Once Daily Long-Acting Formulation of Propranolol with Conventional Propranolol Given Twice Daily in Patients with Mild to Moderate Hypertension

The effect of conventional propranolol tablets given twice daily has been compared with an equivalent dosage of a long-acting formulation of propranolol ('Inderal' LA)p given once daily in twenty-nine patients with mild to moderate hypertension. The study lasted 10 weeks. There was no significant difference in clinical response to the two treatments which were equally effective and well tolerated. A once daily dosage schedule should greatly aid patient compliance.

A combined clinical and immunological assessment of four cyclophosphamide regimes in rheumatoid arthritis

Four dosage regimes of cyclophosphamide have been compared in patients with late rheumatoid arthritis, in an attempt to separate toxicity from efficacy. Joint inflammation was assessed clinically and objectively by quantitative thermography. Delayed hypersensitivity in vitro was assessed using leucocyte migration inhibition (L.M.T.) to a standard antigen, Streptokinase. There was no significant difference in clinical response or side-effects between a continuous oral regime (1 mg/kg/day) and the same total dose given as an intermittent oral regime. Responders and non-responders were seen in both groups and there was a significant relationship between clinical response and fall in platelet count, suggesting a variable threshold. The same total dose given as an intermittent intravenous regime caused considerable side-effects but these could be avoided by the addition of methylprednisolone. Both intravenous regimes induced a much more rapid fall in the Thermographic Index (T.I.) than the oral regimes. Indeed many patients receiving oral cyclophosphamide showed an increase in joint inflammation in the first three weeks of treatment. Immunological studies demonstrated a corresponding increase in reactivity to Streptokinase over this period. There was a highly significant correlation between changes in L.M.T. and T.I. both early in treatment and, in the oral groups, over a period of six months.

Double-Blind Clinical Trials of Oral Cyclacillin and Ampicillin

A double-blind study was performed to compare the clinical response and the incidence of side effects in 2,581 patients administered ampicillin or cyclacillin for infections of the genitourinary or respiratory tract, infections of the skin and soft tissues, or for otitis media. There was no significant difference in clinical response and bacterial eradication. All side effects, including diarrhea and skin rash, were approximately twice as frequent in patients treated with ampicillin.

Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea.

The efficacy of vancomycin in pseudomembranous colitis was assessed in a prospective randomised controlled trial. Forty-four patients with postoperative diarrhoea were allocated to five days' treatment with either 125 mg vancomycin six-hourly or a placebo. Sixteen patients had high titres of the neutralised faecal toxin characteristic of pseudomembranous colitis; nine received vancomycin and seven placebo. At the end of treatment faecal toxins were present in one patient given vancomycin compared with five of the controls. Vancomycin caused the disappearance of Clostridum difficile from the stool in all except one patient, whereas toxicogenic strains of Cl difficile persisted in all but one of the controls. Histological evidence of psuedomembranous colitis had disappeared by the end of treatment in six out of seven patients given vancomycin compared with only one out of seven patients given vancomycin compared with only one out of five patients given placebo. In patients with faecal toxins bowel habit had returned to normal in seven of the vancomycin group compared with only one of the controls, but there was no significant difference in clinical response among patients without faecaal toxins. The results suggest that vancomycin eliminates toxin-producing Cl difficile from the colon and is associated with rapid clinical and histological improvement in patients with pseudomembranous colitis.

Efficacy of clindamycin therapy for otitis media.

A pediatric formulation of clindamycin was evaluated in comparison to ampicillin sodium in treatment of otitis media. Ampicillin and clindamycin were provided in identical numbered bottles and dispensed to 271 children. The randomization procedures employed for assignment of therapeutic regimen yielded two groups which were remarkably similar in relation to age, sex, and clinical severity of disease. No significant differences in clinical response to therapy were observed even when data were evaluated with regard to specific organisms isolated. Clindamycin proved to be effective therapy for otitis media due to penicillin-sensitive and penicillin-resistant Staphylococcus aureus, epidermidis, and Diplococcus pneumoniae . Differences between the two regimens in the response of otitis media caused by Hemophilus influenzae were noted. We would not recommend clindamycin for routine treatment of otitis media caused by H influenzae .