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Biomedical subjects

V Fainstein

Publications and source records attributed to V Fainstein.

At least 73 records · Page 4Linked to original sources

Moxalactam plus ticarcillin or tobramycin for treatment of febrile episodes in neutropenic cancer patients.

Moxalactam disodium in combination with ticarcillin disodium or tobramycin sulfate was used to treat 445 episodes of suspected or confirmed infection in patients with cancer. The majority had leukemia and neutropenia. The rate of cures during the 231 confirmed infections was 65% for moxalactam and ticarcillin and 64% for moxalactam and tobramycin. Both regimens were comparable against aerobic gram-negative and polymicrobial infections. In gram-positive infections, the response rate for moxalactam and ticarcillin was 73% and for moxalactam and tobramycin, 53%. Only three of nine enterococcal infections responded to treatment. Thirteen percent of all organisms recovered were resistant to moxalactam. Side effects occurred infrequently; the most important was coagulopathy due to moxalactam. Nephrotoxic effects occurred in six patients receiving moxalactam and tobramycin and in none of those receiving moxalactam and ticarcillin. In 39 patients, a superinfection was confirmed. Fourteen were fungal, three were due to enterococcus, and one due to Klebsiella species. Eleven of the 14 fungal episodes occurred in the moxalactam-ticarcillin group. Moxalactam with ticarcillin and moxalactam with tobramycin are equally active for the initial treatment of presumed infection in patients with neutropenia.

Adolescent↗

Nonbacterial thrombotic endocarditis in a male homosexual with Kaposi's sarcoma.

Nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, was found at autopsy in a young male homosexual with Kaposi's sarcoma. Vegetations were seen in the mitral and aortic valves. Embolic phenomena and cytomegalovirus infection were noted in the brain, spleen, liver, lung, gastrointestinal tract, and bone marrow. To our knowledge, this is the first reported case of NBTE in a young immunosuppressed homosexual man with Kaposi's sarcoma.

Adult↗

Human cryptosporidiosis: spectrum of disease. Report of six cases and review of the literature.

Although once regarded exclusively as an animal parasite, Cryptosporidium has emerged during the last decade as a cause of diarrhea in humans. Of the 43 cases of human cryptosporidiosis reported, 27 patients in whom either humoral or cell-mediated immune defects were present had chronic protracted diarrhea that was almost invariably unresponsive to therapy and culminated in death. In contrast, 16 patients with intact immune systems had either self-limited disease or were asymptomatic. Animal exposure was almost exclusively recorded in the latter group. During the last six months at University of Texas M. D. Anderson Hospital and Tumor Institute, Houston, gastrointestinal (GI) tract cryptosporidiosis developed in six homosexual men with acquired immune deficiency syndrome (AIDS). The diagnosis of cryptosporidiosis was established histologically in five patients. In four, cryptosporidial oocysts were detected in the stool. In addition to extensive GI tract cryptosporidiosis, two patients had biliary tract involvement. Multiple chemotherapeutic agents failed to control the disease, and five patients eventually died. Cryptosporidiosis should be considered in the differential diagnosis of diarrhea, in animal handlers or in the severely compromised patient, especially one with AIDS, who has chronic protracted diarrhea.

Acquired Immunodeficiency Syndrome↗

In vitro activity of new cephalosporins against multi-resistant gram-negative bacteria.

The in vitro sensitivities of 47 multi-resistant gram-negative bacilli against six third generation cephalosporins were investigated. Overall, moxalactam was the most active compound and cefoperazone the least active. Ceftizoxime and ceftazidime were very active against Enterobacteriaceae. Ceftriaxone and ceftizoxime were active against Escherichia coli and Klebsiella spp., but were inactive against Pseudomonas spp.; Achromobacter sp. was resistant to all drugs, while Citrobacter freundii was sensitive to every antibiotic tested. These drugs may be clinically useful in infections with multi-resistant gram-negative bacteria.

Aeromonas↗

Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B.

The toxicology of liposome-encapsulated amphotericin B in mice and its efficacy in the treatment and prophylaxis of systemic candidiasis in these animals were studied. The toxicology studies indicated that the maximal tolerated dose of free amphotericin B was 0.8 mg/kg of body weight and the 50% lethal dose (LD50) was reached at 1.2 mg/kg, while neither the maximal tolerated dose nor the LD50 for the liposomal amphotericin B was reached at a dose of 12 mg/kg. No abnormalities in blood chemistry or histology were observed in the animals injected with encapsulated amphotericin B, while the administration of free amphotericin B was associated with nephrocalcinosis and renal parenchymal edema. The encapsulated drug was as effective as the free drug when used in similar concentrations, while the animals treated with higher concentrations of liposomal amphotericin B (4 mg/kg) had a longer survival time. Thus, an improved therapeutic index resulted by encapsulating amphotericin B in liposomes.

Amphotericin B↗

Coagulation abnormalities induced by beta-lactam antibiotics in cancer patients.

The records of 714 neutropenic cancer patients who were treated with high doses of a combination of beta-lactam antibiotics were analyzed. In 268 patients, coagulation parameters were measured at least once before, during, and after therapy. Alterations on the prothrombin time, activated partial thromboplastin time, and thrombin time were found in those regimens containing a semisynthetic penicillin, cefamandole, and moxalactam. Mild and severe hemorrhage was observed in some patients receiving these regimens. After prophylactic administration of vitamin K to all patients treated with moxalactam, no further hemorrhage was noted. Alteration of the prothrombin time, with preservation of other parameters, was found in patients receiving antibiotic regimens containing semisynthetic penicillin and cefoxitin. No evidence of hemorrhage was found in this group of patients. In neutropenic cancer patients, the occurrence of another impairment in the clotting process, in addition to thrombocytopenia, greatly increases the risk of serious hemorrhage. Coagulation parameters must be routinely monitored when these patients receive antibiotics known to cause coagulation abnormalities.

Anti-Bacterial Agents↗

Effect of broad-spectrum cephalosporins on the microbial flora of recipients.

The flora in the throat and the stools of 10 patients receiving chemotherapy for malignant diseases in a laminar air-flow room was studied during the prophylactic administration of ceftazidime. Ten percent of aerobic gram-negative bacilli, 41% of aerobic gram-positive organisms, 59% of anaerobes, and 70% of fungi persisted in stool specimens during ceftazidime administration. This drug had a less pronounced effect on the throat flora; 66% of organisms persisted during antibiotic administration. The throat and fecal flora of another eight patients were studied during the prophylactic administration of ceftriaxone. This antibiotic had a profound effect on the fecal flora; none of the gram-negative bacilli, only 24% of aerobic gram-positive organisms, and only 10% of anaerobes persisted during ceftriaxone administration. Like ceftazidime, ceftriaxone had a less marked effect on the throat flora; 59% of organisms persisted during antibiotic administration. The results show that new, expanded-spectrum cephalosporins can have a major suppressive effect on patients' endogenous microbial flora.

Adult↗

A randomized study of ceftazidime compared to ceftazidime and tobramycin for the treatment of infections in cancer patients.

Three hundred and twenty-one febrile episodes in cancer patients were treated with ceftazidime alone or in combination with tobramycin. Patients were grouped according to their neutrophil count into neutropenic and non-neutropenic (less than 1000 and greater than 1000/mm3) respectively. Two hundred and seventy-five episodes were evaluated. The overall response rate in 83 episodes of infection treated with ceftazidime alone was 60 and 73% in those who received the combination. In those bacteriologically proven the response rate was 72% in both groups of the study. The overall response rate in septicaemia was 75% with ceftazidime alone and 85% with the combination. High response rates were obtained in Gram-negative bacillary septicaemias in both groups even in neutropenic patients treated with ceftazidime alone. Pneumonias in neutropenic patients responded equally well. However, patients with adequate neutrophil counts responded better to the combination than to single-agent therapy. The response rate for Gram-positive infections was 41% for ceftazidime alone and 57% for the combination, which was inferior to the results obtained for Gram-negative infections (P = 0.001). The rates of superinfection and toxicity were very low. Ceftazidime is a useful antibiotic against Gram-negative infections in cancer patients. It should be combined with an agent active against Gram-positive pathogens in neutropenic patients.

Adolescent↗

Comparative in vitro study of teichomycin A2.

Teichomycin A2 was evaluated in vitro against clinical isolates, and its activity was compared with that of other antibiotics. This compound was very active against all organisms tested; its activity was comparable to that of vancomycin, and it was superior to several other antibiotics when tested against gram-positive cocci. Because of its in vitro activity, it deserves clinical evaluation.

Anti-Bacterial Agents↗

Effects of hepatic function on vancomycin clinical pharmacology.

Using a recently developed radioimmunoassay, we performed 15 vancomycin pharmacology studies in cancer patients with infections. Vancomycin (500 mg) was infused intravenously for 30 min every 6 h for up to 7 days. The plasma disappearance curve was biphasic, with an initial half-life of less than 30 min. The second half-life (t1/2 beta), not dose related, varied from 1.4 to 231 h among the patients. In six studies of patients with normal hepatic functions, the t1/2 beta was 2.6 h; the rate of total clearance was 162 ml/min. In contrast, nine studies of patients with impaired liver function had a much longer t1/2 beta (37 h) and a decrease in the rate of total clearance to 48 ml/min. These factors resulted in an increase in the value of area under the concentration-time curve from 59 to 3,434 micrograms X h/ml. These results have demonstrated the importance of the effects of liver function on vancomycin disposition. The vancomycin dose and schedule should be adjusted for patients with liver impairment.

Adult↗

Multiple-dose pharmacokinetics of ceftazidime in cancer patients.

The pharmacokinetic parameters of ceftazidime were determined in 25 patients with neoplastic diseases. A group of 13 patients each received 1 g of ceftazidime over 15 min as a single intravenous dose. The mean peak drug concentration in serum was 77.4 micrograms/ml, and the serum half-life was 144 min. Urinary excretion at 12 h was 64.5%. These 13 patients also received 2 g of ceftazidime over 15 min at 8-h intervals for 7 or 8 days. The mean peak drug concentrations in serum were 103.6 micrograms/ml on day 1 and 87 micrograms/ml on day 7 or 8. A second group of 12 patients received 1 g of ceftazidime over 30 min, followed by 1 g over 2 h and every 4 h thereafter. The mean peak drug concentration in serum at 30 min was 57.5 micrograms/ml. Average peak and trough levels obtained on day 2 or 3 were 65 and 34.8 micrograms/ml, respectively, and remained in this range thereafter. The above-mentioned dose schedules produced high and adequate ceftazidime concentrations in serum.

Adolescent↗

Comparative in vitro activities of teichomycin and other antibiotics against JK diphtheroids.

The in vitro susceptibilities of 98 isolates of JK diphtheroids to teichomycin, vancomycin, and eight other antibiotics was investigated. Teichomycin and vancomycin were extremely active against all the isolates tested. The 90% minimal inhibitory concentrations for teichomycin and vancomycin were 1.56 and 0.78 micrograms/ml, respectively. The majority of the isolates were resistant to ticarcillin, methicillin, erythromycin, tetracycline, chloramphenicol, clindamycin, and cephalothin.

Anti-Bacterial Agents↗

In vitro activities of new beta-lactam antibiotics against Acinetobacter spp.

The in vitro activities of new beta-lactam antibiotics was studied and compared with those of other known agents against 51 clinical isolates of Acinetobacter calcoaceticus subsp. anitratus and 23 isolates of A. calcoaceticus subsp. lwoffi. Of the new beta-lactam antibiotics, imipemide (N-formimidoyl thienamycin), ceftazidime, ceftizoxime, ceftriaxone, and piperacillin demonstrated good activities. The minimal inhibitory concentrations for A. calcoaceticus subsp. lwoffi were lower than those obtained for A. calcoaceticus subsp. anitratus.

Acinetobacter↗

Routine use of BACTEC 16B bottles to remove antibacterial and antitumor agents from blood cultures of cancer patients.

A total of 1,764 paired sets of BACTEC 6B and 16B blood culture bottles were collected from patients for analysis. The majority of the patients were receiving antibiotic therapy at the time the blood specimens were collected. A total of 126 isolates were considered clinically significant. Of these, 58 grew in both 6B and 16B bottles, 25 grew only in 6B bottles, and 43 grew only in 16B bottles. In both bottles, the same amount of time was required to detect a positive culture. In 18 patients, septicemias were detected in the 16B bottles that were not detected in the 6B bottles. In seven patients, microorganisms were detected in the 6B bottles that were not detected in the 16B bottles. Interestingly, the antibiotic therapy was changed for only 4 of the 18 patients whose septicemias were detected only in the 16B bottles. Finally, an in vitro study showed that certain chemotherapeutic agents can cause the inhibition of growth of several microorganisms when tested in 6B bottles. These inhibitory effects were reduced or eliminated when the same organism-drug combinations were tested in 16B bottles.

Antineoplastic Agents↗

A comparative in vitro study of thienamycin.

The in vitro activity of thienamycin was compared to that of other antibiotics against a large panel of bacteria obtained in blood cultures from cancer patients. This compound was the most active against gram-positive cocci and also proved to be extremely active against the gram-negative bacteria. It was also very active against multi-resistant gram-negative bacilli. Because of its broad spectrum of activity including Pseudomonas spp., thienamycin deserves clinical testing in the future.

Anti-Bacterial Agents↗