Clarence L. Fortner

A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia.

Fifty-three profoundly granulocytopenic patients with relapsed acute leukemia who were undergoing reinduction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or gentamicin plus nystatin for prevention of infections. The acquisition of new organisms per patient during the total study period was similar in both groups. Thirty-five symptomatic infections (five of which were bacteremias) occurred in patients receiving trimethoprim-sulfamethoxazole plus nystatin, whereas 31 infections (eight bacteremias) occurred in patients receiving gentamicin plus nystatin. Four deaths related to infection occurred in patients taking trimethoprim-sulfamethoxazole, and eight occurred in patients taking gentamicin. We conclude that trimethoprim-sulfamethoxazole plus nystatin was approximately as effective as gentamicin plus nystatin for prophylaxis against infection in relapsed acute leukemia. Furthermore, side effects were fewer and compliance was better with trimethoprim-sulfamethoxazole plus nystatin.

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.

Piperacillin or ticarcillin plus amikacin: A double-blind prospective comparison of empiric antibiotic therapy for febrile granulocytopenic cancer patients

Piperacillin plus amikacin was compared in a prospective randomized double-blind trial with our standard regimen of ticarcillin plus amikacin as empiric therapy of fever in patients with granulocytopenia. Profound persistent granulocytopenia (fewer than 100/microliter polymorphonuclear leukocytes without any rise during therapy) was present in 60 percent of the patient trials in both treatment groups. Of 38 microbiologically and clinically documented infections treated with piperacillin plus amikacin, 22 (58 percent) showed improvement. Of 34 microbiologically and clinically documented infections treated with ticarcillin plus amikacin, 19 (56 percent) showed improvement. There was no difference in response between groups according to the site of infection or infecting pathogen. Toxicity was minimal, with an equivalent incidence of immediate reactions, nephrotoxicity and superinfection. Patients receiving ticarcillin plus amikacin became colonized with more resistant gram-negative bacilli (17) than did those receiving piperacillin plus amikacin (3). Despite the monosodium structure of piperacillin, hypokalemia was not reduced for patients who received piperacillin plus amikacin. Although piperacillin has a wider in vitro antibacterial spectrum than ticarcillin, the clinical efficacy and toxicity of the combination of piperacillin plus amikacin were similar to those of ticarcillin plus amikacin as empiric therapy.

Empiric antibiotic therapy for suspected infection in granulocytopenic cancer patients: A Comparison between the combination of moxalactam plus amikacin and ticarcillin plus amikacin

Moxalactam is a new cephalosporin with a broad spectrum of activity which includes Pseudomonas aeruginosa in addition to Klebsiella species Escherichia coli, and Staphylococcus aureus. Moxalactam was combined with amikacin (M + A) compared to ticarcillin plus amikacin (T + A) in a prospective, randomized double-blind trial of empiric therapy for febrile episodes among granulocytopenic cancer patients. One hundred and ninety-one epidoses were evaluated; T + A, 93 episodes and M + A, 98 episodes. Median granulocyte count of initiation of therapy was less than 100/microliters. Overall response rates were good. In the T + A group, 21 of 29 (72 percent) microbiologically documented infections, including seven of 14 (50 percent) bacteremias, and 24 of 27 (89 percent) clinically documented infections improved. In the M + A group, 20 of 28 (71 percent) microbiologically documented infections, including 11 of 18 (61 percent) bacteremias, and 25 of 25 (96 percent) clinically documented infections resolved. Adverse effects were minimal and equivalent in both groups. Hypokalemia (decrease in serum potassium of greater than 11 mEq/liter from baseline) occurred in 14 of the 93 episodes in the T + A group and in 10 of the 98 episodes in the M + A group with decline in mean serum potassium level of 0.5 and 0.4 mEq/liter respectively. Nephrotoxicity (increase in serum creatinine greater than 0.04 mg/dl) occurred in only one patient in the T + A group and in two patients in the M + A group. Moxalactam plus amikacin has a broader in vitro spectrum, is as effective, and is no more toxic than ticarcillin plus amikacin as empiric therapy for febrile granulocytopenic cancer patients.

Ticarcillin in Combination with Cephalothin or Gentamicin as Empiric Antibiotic Therapy in Granulocytopenic Cancer Patients

Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although Staphylococcus aureus was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by S. aureus but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients.

Potential of mezlocillin as empiric single-agent therapy in febrile granulocytopenic cancer patients.

Mezlocillin was used as an initial empiric antibiotic therapy for febrile (> 101 degrees F, ca. 38.33 degrees C) granulocytopenic (< 1,000/microliter) cancer patients. Patients known to be colonized with an organism resistant to 100 micrograms of mezlocillin per mol were excluded. The initial 25 cases (23 patients) received intravenous mezlocillin, 260 mg per kg per day in six divided doses; the mean 1-h-postinfusion serum level was 69 micrograms/ml. Because of the low serum level, the next 25 cases (22 patients) received 450 mg/kg per day, also in six divided doses, resulting in a mean 1-h-postinfusion serum level of 161 micrograms/ml. Both dosage regimens provided similar efficacy. Combined results show that 11 of 21 microbiologically documented infections and 7 of 13 clinically documented infections improved. Instances of bacteremia (number of cases in parentheses) were caused by Pseudomonas aeruginosa (two), Staphylococcus epidermidis (two), Clostridia perfringens (one), and Bacillus species (one); only one case improved. A rise in granulocyte count to > 500/microliters, a serum bactericidal activity of greater than or equal to 1:8 against the infecting pathogen, or both were indicators of a good therapeutic response. Despite exclusion of patients known to be previously colonized with mezlocillin-resistant organisms, 7 of 23 pathogens required a minimal concentration of greater than or equal to 100 micrograms of mezlocillin per ml for inhibition. In addition, surveillance cultures from 18 cases showed resistant organisms colonizing the gingiva, rectum, or both. Side effects of mezlocillin were minimal and included pseudoproteinuria, asymptomatic transient rise in bilirubin, and easily reversible kypokalemia. Mezlocillin, a new semisynthetic penicillin with little toxicity, was found to be inadequate as a single-agent empiric antibiotic therapy for febrile, granulocytopenic cancer patients.

Comparison of basic infection prevention techniques, with standard room reverse isolation or with reverse isolation plus added air filtration

Abstract Forty-two uninfected, previously untreated patients with acute nonlymphocytic leukemia were randomly allocated to one of three groups to evaluate whether a basic program of infection prevention plus complete reverse isolation with added air filtration (Group I) or the basic program plus reverse isolation without added air filtration (Group II) would be more efficacious for infection prevention than the basic program alone which included a cooked food diet, patient and staff hygiene education and oral nonabsorbable antibiotics (Group III) in a hospital setting with generally excellent environmental controls including filtration of incoming air. The patient populations in the three groups were comparable. Environmental culture results indicated minimal contamination in each of the three settings. There were no substantial differences in new organism acquisition, infection incidence, infection site or pathogen, infectious deaths, hematologic remission or survival among these three groups. We conclude that, in a setting where aquisition and colonization with potential pathogens was kept at a minimum with basic techniques, the added isolation procedures in regular patient rooms were insufficient to further substantially reduce microbial contamination. This suggests that in the current setting of a modern facility, the isolation procedures must be substantially more intensive to further effect a reduction in organism acquisition.

Amikacin and Cephalothin: Empiric Regimen for Granulocytopenic Cancer Patients

Amikacin (15 mg/kg per day) was used in combination with cephalothin (7 g/m2 per day) as an empiric regimen for de novo febrile (>101°F [38.3°C]) episodes in 93 granulocytopenic (<1,000/mm3) cancer patients. Both drugs were given intravenously in four equal doses every 6 h. The response rate for all documented infections was 83%, including 11 of 17 (65%) bacteremias. Escherichia coli (14 cases) was the most common pathogen, whereas Pseudomonas aeruginosa (2 cases) caused fewer infections. Mean amikacin serum levels were 8.7 μg/ml at 1 h and 2.2 μg/ml at 5 h. Failure of bone marrow recovery in association with a bacteremia was a bad prognostic sign (only two of eight improving). Ototoxicity occurred in two (2%) patients, whereas presumed antibiotic-induced nephrotoxicity developed in six (7%) patients. Surveillance cultures (nose, gums axilla, and rectum) of all hospitalized patients revealed no significant change in the incidence of amikacin resistance. The combination of amikacin and cephalothin in this dose and schedule was safe and efficacious in these granulocytopenic patients.

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.

Cost analysis of leukemia treatment: a problem-oriented approach.

A Problem Oriented List of Charges (POLC) can be used to obtain information about the cost of treatment of a single medical problem in patients with several coexisting medical problems. To prepare a POLC, each charge item is associated with one of the patients problems. POLCs were compiled from the Problem Oriented Medical Records (POMRs) of patients with Acute Non‐Lymphocytic Leukemia (ANLL). From the POLCs it was apparent that the treatment of granulocytopenia and thrombocytopenia and their sequelae were the most costly problems associated with ANLL. The projected cost of treatment for all problems for 11.5 months (the median survival of patients with ANLL treated with a single chemotherapeutic agent at this institution) was