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Biomedical subjects

R N Greenberg

Publications and source records attributed to R N Greenberg.

At least 19 recordsLinked to original sources
PubMed1992

Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gram-negative sepsis.

OBJECTIVE: To evaluate the safety and efficacy of E5 (Xomen-E5), a murine monoclonal immunoglobulin M antibody, in reducing mortality in patients with serious Gram-negative infections. Phase II, single-site study. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Surgical, neurosurgical and medical ICUs, comprising approximately 30 beds in a multidisciplinary university hospital. PATIENTS: Patients with clinical evidence of serious infection admitted to the ICU for monitoring of vital signs and for intensive care nursing. Of the 39 patients enrolled in the study, 23 had documented Gram-negative infection. METHODS: Patients suspected of having life-threatening Gram-negative infections received one of two doses of E5 or placebo. Safety and efficacy were assessed by survival on days 3, 7, and 21, appearance of adverse reactions, development of antimurine antibodies, and effects on BP, urine output, WBC count, and temperature. MEASUREMENTS AND MAIN RESULTS: Mortality rate from Gram-negative infection 3 days after the last drug (or placebo) infusion was two (22%) of nine deaths in the placebo group compared with 0 of nine for E5 2.5 mg/kg and 0 of five for E5 7.5 mg/kg. At 21 days after therapy, three patients treated with E5 had died. Only one of these three deaths resulted from infection. Eight of 15 E5 patients tested had immunoglobulin G antimurine antibodies by 3 wks after therapy began, but all were asymptomatic. CONCLUSIONS: E5 was well tolerated and may have the potential to reduce early morbidity and the mortality rate in seriously ill patients with Gram-negative infections. Results from larger phase III studies are needed to confirm these findings.

Acute Disease↗
PubMed1991

Effects of somatostatin analog SMS 201-995 on enterotoxigenic diarrhea.

Somatostatin analog SMS 201-995 causes a dose-related suppression of the release and/or action of several gastrointestinal hormones and impairs several anterior pituitary functions. Some patients with illness involving abnormal hormonal activity have responded to treatment with SMS 201-995, including resolution of severe secretory diarrhea. This study examined SMS 201-995 inhibition of Escherichia coli heat-stable enterotoxin STa (STa) effects and effects of the analog in the rabbit RITARD model with enterotoxigenic Escherichia coli. SMS 201-995 did not alter STa binding to its receptor on piglet brush border membranes. The analog, at concentrations of 0.1 micrograms/ml (0.1 microM) and 1 microgram/ml (1 microM) did not significantly alter STa activation of intestinal epithelial cell particulate guanylate cyclase. At maximal dosing the analog significantly reduced intestinal fluid secretion in suckling mice that was induced by either 8-bromo cyclic GMP or STa. In piglets, the analog reduced by 37-44% the amount of diarrhea induced by STa. However, even with maximal dosing, the piglets still had significant diarrhea, although of a lesser amount. In the rabbit RITARD model the drug failed to alter the severe diarrheal response seen when dosing the animals with enterotoxigenic Escherichia coli. Overall, SMS 201-995 had a significant but incomplete effect in reducing the STa effects seen in the various assays. Additionally, in the RITARD model the analog did not alter the clinical responses to various enterotoxigenic bacteria. SMS 201-995 should be useful as a probe into the mechanisms involved in intestinal fluid secretion, but a clinical role in enterotoxigenic gastrointestinal disease was not supported by this study.

Animals↗
PubMed1991

Randomized, double-blind phase II study of anti-endotoxin antibody (E5) as adjuvant therapy in humans with serious gram-negative infections.

Xomen-E5 (E5) is a murine monoclonal IgM antibody (MAb) that binds to the lipid A epitope of endotoxin. The MAb was developed by immunization against the J5 mutant of Escherichia coli. Prior studies in humans have shown safety and T1/2 of 18.4 hours. In this double blind study patients suspected to have life threatening gram-negative infections were randomized to receive 2 doses, 24 hours apart, of placebo (P), 2.5 mg/kg E5, or 7.5 mg/kg E5. Overall 23 patients had a documented serious gram-negative infection and received at least one dose of study drug. Mortality 3 days after last infusion was 2 of 9 for P, 0 of 9 for 2.5 mg/kg, and 0 of 5 for 7.5 mg/kg. By 21 days after therapy one E5 treated patient had died. Wheezes occurred in one E5 treated patient. Eight of 15 E5 patients treated had IgG anti-murine antibodies by 3 weeks after therapy. These data suggest the need to pursue studies designed to verify that E5 reduced mortality and morbidity in seriously ill patients with gram-negative infections.

Antibodies, Monoclonal↗
PubMed1990

Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin.

Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed.

Adult↗
PubMed1989

Netilmicin sulfate as single-agent therapy for Pseudomonas infections.

In a prospective multicenter clinical trial, 69 patients with Pseudomonas infections were treated with netilmicin sulfate as the only antipseudomonal antibiotic. Clinical resolution or improvement was observed for 81% of the infections, whereas 19% were considered treatment failures. The bacteriologic response, based on follow-up culture results, showed elimination of Pseudomonas from 62% of the infection sites, with persistence in 30%. All isolates were susceptible by disk susceptibility testing (zone greater than or equal to 15 mm), and by microdilution testing in unsupplemented broth. The majority of isolates, however, were resistant in cation supplemented media. The clinical failures could be accounted for by factors other than netilmicin failure. In conclusion, netilmicin appeared effective as treatment for netilmicin-susceptible Pseudomonas infections in nonneutropenic adults. A low incidence of nephrotoxicity (12%) occurred despite careful monitoring of serum levels.

Adult↗
PubMed1987

Randomized trial of ciprofloxacin compared with other antimicrobial therapy in the treatment of osteomyelitis.

Thirty adults (mean age, 52 years) were enrolled in a randomized, comparative trial of oral ciprofloxacin (750 mg twice daily) and other antimicrobial therapies. Etiologic agents included Enterobacteriaceae (18 isolates), Pseudomonas aeruginosa (16 isolates), and Staphylococcus aureus (four isolates). Seven of 14 (50 percent) ciprofloxacin-treated infections are cured at up to 13 months follow-up and three infections appear improved. Treatment failure or relapse has occurred in four patients. Sixteen patients received other antimicrobial therapy and 11 patients (65 percent) remain without infection and have healed wounds, with follow-up from one to 13 months. One patient has had a relapse, while improvement is apparent in four patients. Complications that occurred in this group included drug-related neutropenia (two patients), diarrhea (two patients), drug allergy (one patient), and catheter-related staphylococcal cellulitis (one patient). Oral ciprofloxacin therapy for chronic osteomyelitis caused by susceptible organisms appears to be as effective as other antimicrobial therapies.

Administration, Oral↗
PubMed1987

Treatment of bone, joint, and soft-tissue infections with oral ciprofloxacin.

We treated 52 patients with orally administered ciprofloxacin. In this study of 34 men and 18 women who completed therapy and who could be evaluated, there were 29 patients with nonhematogenous osteomyelitis, 20 patients with skin or soft-tissue infections, and 3 patients with joint infections. During the study, 92 isolates of pathogenic facultative aerobic bacteria, including 37 members of the family Enterobacteriaceae, 30 Staphylococcus aureus isolates, and 21 Pseudomonas aeruginosa isolates, were recovered, and 88 (96%) of the isolates were found to be susceptible to ciprofloxacin. Of the 29 patients with osteomyelitis, 14 have not experienced relapse after a follow-up of at least 1 year. Overall, 61% of infections were resolved, as judged by both clinical and microbiological criteria, during therapy. One patient developed Streptococcus salivarius sepsis during ciprofloxacin therapy, and one patient developed a rash which required discontinuation of ciprofloxacin. Otherwise, there were no serious reactions or complications.

Administration, Oral↗
PubMed1987

Instability of vancomycin in Infusaid drug pump model 100.

The implantable Infusaid drug pump model 100 (Shiley Infusaid, Norwood, Mass.) is undergoing trials as a drug delivery system in the treatment of osteomyelitis. This study evaluated the stability of vancomycin (1 mg/ml) incubated at 37 degrees C for 4 weeks in the pump. Both bioassay and high-pressure liquid chromatography data demonstrated a loss of at least 38% of activity over 4 weeks and colloidal precipitation of vancomycin in the pump at the end of the experiment. This study suggests that vancomycin is not stable enough for use in the Infusaid drug pump model 100.

Drug Stability↗
PubMed1987

Comparison trial of clindamycin with aztreonam or gentamicin in the treatment of postpartum endometritis.

Sixty-two patients who had postpartum endometritis were treated with clindamycin in combination with either aztreonam or the aminoglycoside gentamicin. Currently, the combination of clindamycin and an aminoglycoside constitutes a treatment of choice for this condition. Our results suggest that aztreonam can be substituted for an aminoglycoside in the treatment of postpartum endometritis with similar clinical outcomes.

Adolescent↗
PubMed1987

Cefoperazone-sulbactam combination in the treatment of urinary tract infections: efficacy, safety, and effects on coagulation.

Seventy hospitalized patients with upper urinary tract infections were treated with cefoperazone (2 gm) and sulbactam (1 gm) every 12 hours for three or more days. All but six patients also received vitamin K. Forty of the 70 patients (57%) were cured of infection at one week after treatment, 13 relapsed, 11 had reinfections, and six were lost to follow-up. There were no treatment failures. Escherichia coli was the predominant pathogen (62% of isolates). Overall there was 15% resistance to cefoperazone and all resistant isolates were susceptible to the combination of agents. Synergy was demonstrated in 26% of isolates. One uroseptic patient who had an organism resistant to both study agents, but susceptible to the combination, was cured. Two of six patients who did not receive vitamin K demonstrated abnormal coagulation patterns and one had an associated major bleeding complication. Although 12 of 64 (19%) patients who received vitamin K had at least one coagulation abnormality, there were no significant bleeding complications in this group.

Adolescent↗
PubMed1986

Antibiotic stability in an implantable pump.

We measured the stability of vancomycin, amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam in an implantable drug pump. Two pumps were filled with the antibiotic being tested and were incubated at 37 degrees for 3 weeks. Samples were taken daily. At 3 weeks the pumps were disassembled and examined microscopically for signs of deterioration. If the pumps were intact, bioassays were used to quantitate the biologic activity of each daily antibiotic sample. Vancomycin degraded the pump. Amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam had no effect on the pump and maintained their biologic activity over the 3-week period.

Amikacin↗
PubMed1986

Randomized study of single-dose, three-day, and seven-day treatment of cystitis in women.

We evaluated the following five treatment regimens for acute cystitis in nonpregnant women: cefadroxil, 1,000 mg single-dose; cefadroxil, 500 mg twice a day for three days; cefadroxil, 500 mg twice a day for seven days; trimethoprim-sulfamethoxazole (TMP-SMZ), 320-1,600 mg single-dose, and TMP-SMZ, 160-800 mg twice a day for three days. At four weeks after the end of treatment, 25%, 58%, 70%, 65%, and 88% of patients, respectively, remained cured of infection. The results indicated that three-day treatment (1) might improve cure rates (over single-dose), (2) would reduce incidence of relapse (vs. single-dose), and (3) may be as curative as seven-day treatment. The results of the antibody-coated bacteria test did not predict treatment failure or relapse.

Administration, Oral↗
PubMed1986

Characterization of heat-stable enterotoxin from a hypertoxigenic Escherichia coli strain that is pathogenic for cattle.

An enterotoxigenic Escherichia coli (ETEC) strain isolated from a calf with clinical scours was found to produce over 17- to 60-fold more heat-stable enterotoxin (STa) than four laboratory-adapted bovine ETEC strains. The purified STa of this strain was identical to those produced by other ETEC strains. A severe form of scours was induced in 5- to 15-day-old colostrum-fed calves and in 1- to 2-week-old piglets by oral administration of the purified STa. This study demonstrates that STa is a mediator of diarrhea in newborn calves and piglets and that under identical growth conditions diverse strains of bovine ETEC may produce variable amounts of homologous STa's.

Amino Acid Sequence↗
PubMed1986

Synergistic activity of amikacin with aztreonam against Pseudomonas aeruginosa and other gram-negative organisms.

The effects of amikacin in combination with aztreonam were tested on 100 strains of gram-negative bacteria by means of the microtiter checkerboard system. Eighty-one strains were Pseudomonas aeruginosa, eight were Enterobacter species, seven were Acinetobacter species, two were Alcaligenes species, one was a Citrobacter organism, and one was Pseudomonas stutzeri. All strains had a minimal inhibitory concentration (MIC) to aztreonam between 4 and 256 micrograms/ml (MIC50 = 16 micrograms/ml) and an MIC to amikacin between 8 and greater than 128 micrograms/ml (MIC50 = 16 micrograms/ml). A synergistic effect (fourfold less MIC when both aztreonam and amikacin were present) was observed for 40 (49%) of 81 P aeruginosa and three (16%) of 19 of the other strains tested. All the remaining test strains showed an additive response; no antagonism was observed. The MICs to aztreonam and to amikacin for 98% of strains that exhibited synergism ranged from 2 to 32 micrograms/ml.

Amikacin↗