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Biomedical subjects

S C Schimpff

Publications and source records attributed to S C Schimpff.

At least 109 records · Page 6Linked to original sources

Randomized trial of empiric antibiotic therapy with ticarcillin in combination with gentamicin, amikacin or netilmicin in febrile patients with granulocytopenia and cancer.

A randomized trial of ticarcillin plus gentamicin (group 1), ticarcillin plus amikacin (group 2) and ticarcillin plus netilmicin (group 3) as empiric antibiotic therapy in patients with granulocytopenia and cancer was carried out at the Baltimore Cancer Research Center. The response rate for all infections was 97 per cent in group 1, 91 per cent in group 2 and 95 per cent in group 3. Patients with bacteremias showed improvement in 93 per cent (group 1), 78 per cent (group 2) and 82 per cent (group 3) of cases. All failures were among patients with gram-negative bacteremias. Both antibiotic susceptibility of the bacteremic organism and granulocyte recovery correlated with patient improvement. Nephrotoxicity and ototoxicity were rare and were not significantly different in three groups of patients. Therefore, ticarcillin plus gentamicin, ticarcillin plus amikacin and ticarcillin plus netilmicin appear to be equally efficacious and minimally toxic in this patient population. Excellent over-all results can be expected with these combinations provided the etiologic agent is susceptible.

Adolescent↗

Role of vancomycin as a component of oral nonabsorbable antibiotics for microbial suppression in leukemic patients.

A total of 38 adult patients with acute leukemia who were undergoing remission induction chemotherapy in regular patient rooms were randomly allocated to one of two oral nonabsorbable antibiotic regimens for infection prophylaxis (gentamicin, vancomycin, and nystatin [GVN] or gentamicin and nystatin [GN]) to evaluate whether vancomycin was a necessary component. The patient population in both groups were comparable. Tolerance to GVN was less than GN but compliance was approximately equal (>85% in both groups). Patients receiving vancomycin demonstrated greater overall alimentary tract microbial suppression; however, acquisition of potential pathogens was approximately equal in both groups. The incidence of bacteremia, as well as the overall incidence of infection as related to the number of days at various granulocyte levels, was also approximately equal in both groups. Group D Streptococcus species were poorly suppressed by GN compared with GVN, although no patient developed an infection with these organisms. Colonization by newly acquired gram-negative bacilli was significantly less in the GN group (GN, 3 colonizations; GVN, 13 colonizations; P < 0.01). It is concluded that vancomycin may be safely eliminated from the GVN regimen provided microbiological data is monitored to detect resistant organisms.

Adult↗

Invasive aspergillosis in acute leukemia: correlation with nose cultures and antibiotic use.

Aspergillosis in cancer patients is a problem. Because not all patients can undergo invasive procedures, we sought other methods for diagnosis. We reviewed the data from all patients with acute nonlymphocytic leukemia treated at our center during a 3-year period. Of 125 patients, 18 had invasive aspergillosis (cases). Eleven patients had nose cultures growing Aspergillus flavus or A. fumigatus; 10 of these 11 had aspergillosis, whereas only eight of 114 without such nose cultures had invasive disease (P less than 0.000001). Thus, A. flavus on nose culture appears "predictive" for aspergillosis. Absence of such a culture does not preclude infection. Of 125 patients, 61 had sterile nose culture(s) and 14 of the 18 cases had such a sterile nose culture. Only four of the 64 patients without sterile nose cultures developed aspergillosis (P less than 0.008), suggesting a relation between sterile nose culture and aspergillosis. Carbenicillin was used for a longer period among cases and patients with predictive nose cultures than among patients without aspergillosis. These data may help identify patients at risk of aspergillosis and help determine antifungal therapy when invasive procedures are contraindicated.

Acute Disease↗

Alloimmunization following prophylactic granulocyte transfusion.

Nineteen noninfected adults receiving initial induction chemotherapy for acute nonlymphocytic leukemia (ANLL) were randomized to receive either prophylactic granulocyte transfusion or platelet transfusion alone on an alternate-day schedule. An average of 11 granulocyte transfusions (range 3--19) were administered/patient with a mean dose of 11.5 X 10(9) granulocytes/transfusion. The groups were identical with respect to age, sex, number of days on study, granulocytopenic days, percent of days receiving systemic antibiotics, febrile days, complete remission rate, and incidence of minor infection. Significant transfusion reactions were much increased in the granulocyte transfusion group (7/10 versus 1/9 in controls) and were associated with the development of lymphocytotoxic antibodies (7/10 versus 4/9 controls), refractoriness to platelet transfusion, repeated fevers, and a pulmonary infiltrate in one patient. Alloimmunization to granulocytes occurred as early as the second week in some patients complicating platelet support during induction and maintenance. No severe infections occurred in the granulocyte transfusion group while three fungal infections occurred in the controls. The high rate of alloimmunization suggests that histocompatibility considerations indicate that prophylactic granulocyte transfusion should not be routine therapy and should be studied only in investigational settings.

Acute Disease↗

Comparative auditory toxicity of aminoglycoside antibiotics in leukopenic patients.

The incidence of auditory toxicity resulting from therapy with ticarcillin (T) (12 g/sq m/day) in combination with gentamicin (G) (200 mg/sq m/day), amikacin (A) (600 mg/dq m/day), or netilmicin (N) (280 mg/sq m/day) was compared. Before administration of these antibiotic combinations to febrile, granulocytopenic patients, baseline audiograms were determined by a pharmacist using a portable audiometer. The before-therapy audiograms for 32 patients receiving T and G, 29 receiving T and A, and 29 receiving T and N were compared with the audiograms after the completion of therapy. The mean length of therapy was seven days. Two patients (6.2%) receiving T and G, one (3.4%) receiving T and N, and one (3.4%) receiving T and A developed auditory toxicity with bilateral decreases of at least 20 decibels at one or more frequencies. The incidence of auditory toxicity secondary to aminoglycoside exposure was low, and the relative auditory toxicity among the three aminoglycosides appeared to be similar.

Agranulocytosis↗

Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections.

Acute Disease↗

Comparison of serum bactericidal activity among three antimicrobial combinations.

Three antimicrobial combinations, ticarcillin plus cephalothin (T+C), ticarcillin plus gentamicin (T+G), and cephalothin plus gentamicin (C+G), were administered to 105 febrile granulocytopenic cancer patients at the Baltimore Cancer Research Center as part of a multi-institutional prospective randomized antibiotic trial. The sera from 32 of these patients (T+C-10 patients, T+G-10 patients, and C+G-12 patients) obtained 1 h post-antibiotic administration were examined for bactericidal activity against 11 strains each of the most common pathogens infecting the granulocytopenic host: Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Each of the three antibiotic regimens produced a high degree of bactericidal activity in these sera against S. aureus and E. coli. P. aeruginosa was equally, although poorly, killed by sera containing ticarcillin (T+G, T+C), whereas C+G produced no measurable serocidal activity (P < 0.05). Sera with C+G killed K. pneumoniae more effectively than T+G; T+C produced the least killing effect of the three regimens against this organism (P < 0.05). The bactericidal activity of the serum from these 32 patients supplements the overall clinical results of the multi-institutional antibiotic trial and suggests that T+G is a useful initial regimen for empiric therapy of febrile episodes in granulocytopenic cancer patients.

Anti-Bacterial Agents↗

Effect of two cancer chemotherapeutic agents on the antibacterial activity of three antimicrobial agents.

Cancer chemotherapeutic agents and antibacterial antibiotics are often given concomitantly. Daunorubicin, cytosine arabinoside, and three antibiotics (gentamicin, amikacin, and ticarcillin) were tested individually and in combinations to determine their antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. These cytotoxic agents are commonly employed in the therapy of acute nonlymphocytic leukemia for remission induction therapy, and these antimicrobial agents are used in infection therapy. The maximum concentrations of the two cytotoxic drugs were chosen to be twice the known peak plasma levels of commonly employed dosage schedules. Neither of the cancer chemotherapeutic agents, alone or in combination, demonstrated bactericidal activity at the levels tested. However, in the presence of these agents, the antimicrobial activity of gentamicin and amikacin, although not that of ticarcillin, was depressed for 11 of 15 K. pneumoniae strains and 8 of 15 P. aeruginosa strains, but for none of the strains of E. coli. This level of decreased activity occasionally resulted in a minimal inhibitory concentration of the tested aminoglycoside well above the standard serum levels. Daunorubicin was more likely to antagonize gentamicin than was cytosine arabinoside.

Amikacin↗

Herpes zoster and impaired cell-associated immunity to the varicella-zoster virus in patients with Hodgkin's disease.

Thirty-two patients with Hodgkin's disease and 12 normal donors were studied for their in vitro lymphocyte responsiveness to a membrane-associated varicella-zoster (VZ) antigen. When compared to the normal donors, patients with Hodgkin's disease in whom radiotherapy was recently completed and those with active, recurrent disease had markedly impaired cell-associated immunity to VZ antigen. In addition, there was a suggestion that patients in long-term remission who had received primary combined modality therapy (radiotherapy plus chemotherapy) had an impaired response when compared to normal persons or to patients who had received single modality therapy. Newly diagnosed, untreated patients with Hodgkin's disease did not differ significantly from normal persons as a group but two of six were unresponsive to the VZ antigen whereas all normal subjects were responsive. Most patients in remission for at least one year following therapy had normal in vitro responsiveness. In two patients herpes zoster developed after the demonstration of absent in vitro lymphocyte reactivity to the VZ antigen.

Adult↗