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Biomedical subjects

M D Appleman

Publications and source records attributed to M D Appleman.

At least 37 records · Page 2Linked to original sources

Intraoperative concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue.

To evaluate concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue after intravenous administration, patients greater than or equal to 16 years old diagnosed with acute cholecystitis were randomly assigned to receive ofloxacin (400 mg) intravenously every 12 h or ceftazidime (2 g) intravenously every 8 h. Doses of each regimen were given preoperatively. Serum, bile fluid, and gallbladder wall tissue samples of consecutive patients in the ofloxacin group were obtained intraoperatively. The samples were frozen at -70 degrees C until analyzed by high-pressure liquid chromatography. Twenty-three patients (6 males and 17 females) were evaluated. The mean (+/- the standard deviation) ofloxacin concentrations in serum, bile fluid, and gallbladder wall tissue were 2.9 +/- 2.4 and 6.0 +/- 7.9 micrograms/ml and 3.1 +/- 2.9 micrograms/g, respectively. The mean number of doses each patient received before surgery was 5.3 +/- 3.0, and the mean delta time (time elapsed between last antibiotic administration and when intraoperative samples were obtained) was 9.6 +/- 7.5 h. The mean tissue-to-serum ratio was 1.2 +/- 0.5, and the mean bile-to-serum ratio was 2.3 +/- 1.4. The mean serum ofloxacin concentrations were not statistically different from the concentrations in bile (P = 0.1) and tissue (P = 0.7) at the mean delta time. The study revealed that concentrations of ofloxacin in serum, bile fluid, and gallbladder tissue after intravenous dosing were adequate against susceptible organisms found in the biliary tract.

Adult↗

Treatment of intra-abdominal infections: cost comparison of ampicillin/sulbactam and clindamycin/gentamicin.

The cost of 2 g ampicillin/1 g sulbactam given IV piggyback qid was compared with 900 mg clindamycin admixed with 1.5 mg/kg gentamicin given IV piggyback tid for the treatment of perforated or gangrenous appendicitis in 116 patients. Fifty-eight ampicillin/sulbactam-receiving patients incurred greater costs for IV supplies (+104.6/patient vs +67.9/patient) and nursing administration costs (+16.5/patient vs +10.7/patient). On the other hand, pharmacist and technician preparation costs were greater for the 58 clindamycin/gentamicin-receiving patients (+15.4/patient vs +13.3/patient). The clindamycin/gentamicin-receiving patients also incurred additional changes for laboratory fees and pharmacokinetic monitoring--+18.7/patient and +36.1/patient, respectively. When incorporating all cost parameters, there were no statistically significant differences in mean total drug therapy costs between the two treatment regimens--+433.3 +/- +58.5/patient for ampicillin/sulbactam and +373.8 +/- +86.2/patient for clindamycin/gentamicin.

Ampicillin↗

Ceftazidime/clindamycin versus tobramycin/clindamycin in the treatment of intra-abdominal infections.

In order to assess the efficacy and toxicity of ceftazidime as a substitute for aminoglycosides in the treatment of intra-abdominal sepsis, a prospective randomized trial was conducted. Ninety-four patients (49% trauma) were randomized to receive ceftazidime/clindamycin (CAZ/C) (n = 47) or tobramycin/clindamycin (T/C) (n = 47). CAZ (2.0 gm) and C (0.9 gm) were administered intravenously every 8 hours while T dosage was adjusted to maintain peak (5-8 mg/L) and trough (less than 2 mg/L) concentrations. Age, sex, baseline serum creatinine, and etiology of infection were comparable in the two groups. Clinical cure was similar in culture-positive and culture-negative patients who received CAZ/C (94% vs 88%). The clinical cure rate however was significantly lower in the T/C culture positive (73%) than in the culture negative patients (100%) (P = 0.016). Pathogenic organisms were eradicated in 100% (30/30) and 76% (13/17) of CAZ/C and T/C patients, respectively (P = 0.0006). Nephrotoxicity Nephrotoxicity or ototoxicity was observed in none of the CAZ/C patients and in one and two T/C patients, respectively. CAZ/C more effectively eradicated the bacteria isolated from these patients and no significant difference in clinical response was observed in culture-positive patients. These findings plus the lack of toxicity suggest that CAZ/C is an effective alternative for treatment of IAI.

Abdomen↗

Controlled comparison of cefmetazole with cefoxitin for prophylaxis in elective cholecystectomy.

Prophylactic antibiotics are given routinely to patients undergoing surgical treatment of the biliary tract to prevent postoperative infection if risk factors for postoperative sepsis are present. Cefmetazole (CM) is a new broad spectrum parenteral cephamycin antibiotic. This drug possesses a spectrum of activity against a wide range of gram-negative and gram-positive bacteria that is similar to cefoxitin (CX), an antibiotic widely used for prophylaxis with operations upon the abdomen. In this study, there was a random selection of two patients to receive CM to every one patient to receive CX. The dose of CM was 1 gram given intravenously every eight hours for three doses beginning 30 minutes before the operation; three doses of CX were given intravenously, 2 grams every six hours. Fifty-two evaluable patients comprised the CM group and 26, the CX group. The risk factors for postoperative infection were acute cholecystitis (CM, seven patients; CX, one patient), evidence from imaging procedure suggesting need for exploration of the common duct (CM, six; CX, one), hyperbilirubinemia (CM, eight; CX, four), hyperamylasemia (CM, 17; CX, seven); age of 60 years or more (CM, six; CX, one), obesity (CM, 36; CX, 14) and diabetes mellitus (CM, four; CX, five). Operative bactibilia and the organisms were comparable in both groups. Postoperative days of fever greater than or equal to 38 degrees C. (oral) (CM, 0.83 +/- 1.20; CX, 0.58 +/- 0.96) and hospitalization (CM, 6.59 +/- 2.20; CX, 5.04 +/- 1.26) were similar. Postoperative septic complications at the operative site occurred in two patients in the CM group (4 per cent) and in none of the patients in the CX group (p = 0.4; N.S., Fischer exact test). These two antibiotics had similar efficiency in preventing postoperative infections.

Adult↗

Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons.

We estimated the prevalences of Helicobacter pylori (formerly called Campylobacter pylori) infection and histologic gastritis in 113 asymptomatic persons, using endoscopic biopsy of the gastric antrum and corpus. Unsuspected lesions, mainly mucosal erosions, were revealed at endoscopy in 16 subjects (14 percent). Gastritis was found in 42 subjects (37 percent), of whom 36 (32 percent of the total) were found to be infected with H. pylori on the basis of hematoxylin-eosin staining. H. pylori was not found in any of the 71 subjects with normal histologic features. Gastritis and H. pylori were noted in both the antrum and corpus in 75 percent of those infected (n = 27). The prevalence of H. pylori infection increased from 10 percent (2 of 20 subjects) in those between the ages of 18 and 29, to 47 percent (7 of 15) in those between the ages of 60 and 69, but the effect of age did not reach statistical significance. The prevalence of gastritis increased significantly with advancing age. Stepwise logistic regression analysis revealed that the relative risk for H. pylori infection associated with recent (within six months) antibiotic use was 5.8 (95 percent confidence interval, 1.5 to 22.1), whereas the relative risk was 6.5 (95 percent confidence interval, 1.4 to 29.2) for those who had never used bismuth compounds. We conclude that histologic gastritis and H. pylori infection commonly occur in the stomach of apparently normal persons and increase in prevalence with advancing age. All the subjects with H. pylori infection had gastritis, suggesting a possible etiologic role for the bacterium in the histologic lesion.

Adolescent↗

Cost analysis of two clindamycin dosing regimens.

A clinical trial of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg (eight-hourly group) versus clindamycin 600 mg q6h with gentamicin 1.5 mg/kg given separately (six-hourly group) was analyzed for relative cost containment. Acquisition costs were significantly higher for the six-hourly group for intravenous supplies ($181.5 +/- 47.8) when compared with the eight-hourly group ($67.6 +/- 21.6) (p less than 0.05). Nursing administration costs were greater for the six-hourly group ($28.6 +/- 7.5) compared with ($10.7 +/- 3.4) for the eight-hourly group (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for pharmacist and technician manufacturing cost for the six-hourly group ($15.4 +/- 4.0) compared with the eight-hourly group ($13.3 +/- 4.3). Incorporating all appropriate costs, the mean total drug therapy costs were significantly greater (p less than 0.05) for clindamycin 600 mg q6h ($527.4 +/- 143.0) compared with clindamycin 900 mg q8h ($433.3 +/- 99.2). The dosing of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg is a more cost-effective method of drug delivery with similar efficacy and safety when compared with clindamycin 600 mg q6h with gentamicin given separately.

California↗

A cost comparison of intramuscular versus intravenous imipenem.

Previously reported clinical trials of imipenem-cilastatin 500 mg given intravenously every 6 hours (intravenous group) and imipenem-cilastatin 750 mg given intramuscularly every 12 hours (intramuscular group) were analyzed for relative cost savings. Acquisition costs were significantly higher for the intravenous group for intravenous supplies (30.6 +/- 7.9 dollars) when compared to the intramuscular group (0.98 +/- 0.03 dollars) (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for salaries of pharmacists and technicians for manufacturing in the intravenous group (5.8 +/- 1.5 dollars) as compared to the intramuscular group (2.4 +/- 0.7 dollars). Nursing administration costs were greater for the intramuscular group (15.6 +/- 4.8 dollars) when compared to the intravenous group (11.7 +/- 3.0 dollars). Incorporating all appropriate costs, the mean total drug therapy costs (TRX$) were significantly greater (p less than 0.01) for the intravenous group (458.17 +/- 175.17 dollars) as compared to the intramuscular group (298.0 +/- 114.76 dollars). Thus, the dosing of imipenem-cilastatin 750 mg intramuscularly every 12 hours is a more cost effective method of drug delivery with equal efficacy and safety when compared to imipenem-cilastatin 500 mg given intravenously every 6 hours.

Adolescent↗

Evaluation of two different dosage regimens of clindamycin and the penetration into human appendix.

The study objective was to evaluate serum, peritoneal fluid, and appendix tissue concentrations of clindamycin using two differing clindamycin regimens. Patients age 16 years and older who were about to undergo appendectomies were randomly assigned to receive gentamicin 1.5 mg/kg every 8 h admixed with clindamycin 900 mg every 8 h (8-h group) or clindamycin 600 mg every 6 h given separately (6-h group). Doses of each regimen were given preoperatively. Serum, peritoneal fluid, and appendix tissue samples were obtained intraoperatively, and frozen at -70 degrees C for gas chromatographic drug analysis. Twenty-one patients were evaluated, 11 patients in the 8-h group and 10 patients in the 6-h group. Values are reported as means +/- standard deviations. The values in the 8-h group were 12.3 +/- 14.1 micrograms/ml, 8.7 +/- 3.9 micrograms/ml, and 9.8 +/- 10.3 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The values in the 6-h group were 9.7 +/- 5.1 micrograms/ml, 5.8 +/- 5.3 micrograms/ml, and 6.2 +/- 4.9 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The 6-h group received more doses preoperatively (1.8 +/- 0.6) than the 8-h group (1.2 +/- 0.4; p less than 0.05). No differences in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue for the 8-h group and the 6-h group were noted. The study revealed a similarity in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue using either clindamycin 900 mg given by intermittent intravenous infusion every 8 h admixed with gentamicin or clindamycin 600 mg given every 6-h separately.

Adolescent↗

Prevalence of Campylobacter pylori and association with antral mucosal histology in subjects with and without upper gastrointestinal symptoms.

To determine the incidence and significance of Campylobacter pylori in patients undergoing routine endoscopic evaluation at this hospital, biopsies of the antrum were obtained from 132 patients and from 15 asymptomatic volunteers. Specimens were cultured and silver stained for the presence of C. pylori and were examined histologically. C. pylori was detected in 67 (51%) patients and two (13%) volunteers (P = 0.006). In patients, C. pylori was found significantly more often when the mucosa was inflamed (67%) than when the mucosa was normal (13%), and both volunteers with C. pylori had chronic gastritis on histological examination. When compared to the volunteers, patients with upper gastrointestinal symptoms had a significantly increased prevalence of antral inflammation, even if the endoscopic examination was normal. C. pylori is infrequently found in young asymptomatic adults but is found in both asymptomatic volunteers and patients in association with all forms of histological antral gastritis which is prevalent in patients with both normal endoscopic findings and peptic ulcer disease.

Adult↗

Prevalence of gastric metaplasia, inflammation, and Campylobacter pylori in the duodenum of members of a normal population.

Mucosal biopsies were obtained from 116 asymptomatic volunteers (50% were male; mean age, 46 years; age range, 19-91 years) to study the prevalence of duodenal gastric metaplasia (GM) and its association with inflammation and Campylobacter pylori in a normal population. GM was identified in 25 subjects (22%). Eighty-three subjects (72%) had histologic duodenitis, but in only 10 did the infiltrate include neutrophils (grade 2 duodenitis). C. pylori was found in the stomach in 36 subjects (31%), all of whom had gastritis, but was not identified histologically in the duodenum. There were no significant differences between the overall frequency of duodenitis and either GM or antral C. pylori. Although the frequency of severe (grade 2) duodenitis was not significantly different between those with and those without GM, grade 2 duodenitis was found in 9 of 36 subjects with antral C. pylori but in only 1 of 80 without antral C. pylori (P less than 0.001). These findings suggest that gastric metaplasia is a common finding in the normal population and that grade 1 duodenitis is most likely clinically unimportant, whereas grade 2 duodenitis is usually associated with antral C. pylori.

Adult↗

Detection of cytomegalovirus DNA in peripheral blood of patients infected with human immunodeficiency virus.

Detection of cytomegalovirus (CMV) DNA can be facilitated by the polymerase chain reaction (PCR), an in vitro gene amplification technique. Twenty-eight CMV tissue culture isolates were examined by amplification of two separate CMV genes. All were found to contain CMV, although two of the isolates were positive for only one of the two genes. No detectable amplification occurred with human genomic or other viral DNA controls. The amplification products from as few as one CMV plaque-forming unit could be detected after the PCR. CMV DNA was detected in the blood of 14 of 27 patients with AIDS and one of six patients who were infected with human immunodeficiency virus but who did not have AIDS. Normal CMV-seropositive or -seronegative individuals did not have CMV DNA detected in their blood. The CMV PCR was more sensitive than the standard culture assay, can be completed in one to two days, uses only 20 microL of blood, and may be useful for rapidly detecting CMV in clinical specimens.

Acquired Immunodeficiency Syndrome↗

Norfloxacin in the eradication of enteric infections in AIDS patients.

Recurrent episodes of salmonellosis, including recurrent life-threatening bacteremias, have been well-described in patients with AIDS. Because of the need to avoid sensitization to trimethoprim-sulfamethoxazole (TMP-SFX) in AIDS patients and the high frequency of ampicillin resistance of Salmonella isolates, alternative therapies must be sought. We report the treatment of nine AIDS patients, who had recurrent salmonellosis, with norfloxacin, a new oral fluoroquinolone which has excellent in vivo activity against Salmonella sp. Each patient had two to three prior distinct clinical episodes of salmonellosis which had failed to be eradicated with standard courses of ampicillin, TMP-SFX, ceftriaxone or cefotaxime. Microbiologic relapse had occurred in each patient within 2-4 weeks. Each of the enteric pathogens was susceptible in vitro to norfloxacin. Patients were treated with norfloxacin 400 mg bid orally for 30 days. Stool cultures were negative at 1 week in all patients. Nausea and headache were the only adverse reactions to norfloxacin noted. One patient had a clinical and microbiologic relapse of Salmonella 1 week after norfloxacin was stopped but responded to retreatment with norfloxacin. Norfloxacin appears effective in the treatment of enteric infections in AIDS patients and may be more useful than standard agents in eradicating the organism and preventing clinical and microbiologic relapse. Oral administration and twice daily dosing are significant advantages.

Acquired Immunodeficiency Syndrome↗

Potential of topical norfloxacin therapy. Comparative in vitro activity against clinical ocular bacterial isolates.

Norfloxacin, a new fluoroquinolone antibiotic related to nalidixic acid, was evaluated as a topical agent for clinical efficacy in bacterial eye infections. This study reports on the comparative in vitro activity of norfloxacin and ten topical antibiotics (nalidixic acid, polymyxin B, colistin, bacitracin, chloramphenicol, sulfamethoxazole, tetracycline, erythromycin, gentamicin, and tobramycin) against 203 pathogenic eye isolates of 17 genera (37 species). In general, norfloxacin had the greatest potency and broadest spectrum of activity of the agents tested. It was active against Staphylococcus aureus (minimal inhibitory concentration against 90% [MIC90], less than or equal to 1.0 microgram/mL), coagulase-negative staphylococci (MIC90, less than or equal to 1.0 microgram/mL), Pseudomonas aeruginosa (MIC90, less than or equal to 1.0 microgram/mL), and Haemophilus organisms (MIC90, less than or equal to 1.0 microgram/mL).

Administration, Topical↗

Surgically treated gangrenous or perforated appendicitis. A comparison of aztreonam and clindamycin versus gentamicin and clindamycin.

A randomized, double-blinded, controlled clinical study of 84 patients with surgically treated gangrenous or perforated appendicitis was done to compare the efficacy of the combination of aztreonam, the first monobactam antibiotic, with gentamicin when either was combined with clindamycin. Fifty-six patients who were treated with aztreonam and clindamycin (A/C) and 28 patients who were treated with gentamicin and clindamycin (G/C) fulfilled criteria for evaluation. A matched historic control group of 56 G/C patients was also included for comparison. All measures of outcome, including days of fever, hospitalization, antibiotic therapy, and the incidence of antibiotic failures, were similar. It was concluded that aztreonam was as effective as gentamicin in this study and may offer some advantages with regard to toxicity and serum drug level monitoring.

Adult↗

Cost analysis of antibiotics in the management of perforated or gangrenous appendicitis.

Costs associated with treating patients for gangrenous or perforated appendicitis were compared. Patients received single agent therapy with cefoperazone or cefamandole or combination antibiotics consisting of clindamycin and serum level-adjusted gentamicin. Forty-eight patients received cefamandole, 47 received cefoperazone, and 52 received combination clindamycin and gentamicin. Costs to the pharmacy for drugs were greater for the combination therapy; however, the higher failure rate associated with the cephalosporins created greater expenses for the single agent therapy than for combination therapy.

Adolescent↗

The efficacy of cefoxitin vs. clindamycin/gentamicin in surgically treated stab wounds of the bowel.

A randomized, double-blind study of cefoxitin (CX) or clindamycin/gentamicin (CG) as adjuncts to the surgical management of peritonitis is reported. Groups with similar infection risks were evaluated by including only patients with abdominal stab wounds, enteric injury, and spillage of the gastrointestinal contents. One hundred ninety-five patients were entered of whom 75 were evaluable. Comparisons of the ages, sex, diagnoses, and measures of outcome were not significantly different. Fifteen per cent (5/34) of CX treated patients had postoperative complications (three infections) vs. 10% (4/41) of patients treated with CG (three infections). Intraperitoneal bacteria were cultured from 62% of CX and 59% of CG patients. Antibiotic resistance, seen in three patients of each group, was not associated with failure. Two moderately sensitive Bacteroides distasonis were each associated with a failure in the CX and CG groups. We deduce that both regimens are effective and that cefoxitin may represent less costly single-agent therapy.

Adolescent↗