ro13-9904 and Agranulocytosis

Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost.. In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less.. Equivalence was demonstrated at the second interim analysis, and the trial was terminated after the enrollment of 353 patients. In the analysis of the 312 patients who were treated according to the protocol and who could be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confidence interval, 78 to 90 percent; P=0.02). The results were similar in the intention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency.. In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Amikacin; Amoxicillin; Antineoplastic Agents; Bacteremia; Ceftriaxone; Child; Child, Preschool; Ciprofloxacin; Clavulanic Acid; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Prospective Studies; Survival Rate

Clinical efficacy of 3rd generation cephalosporins i.e. oral cefpodoxime and parenteral ceftriaxone was studied in the treatment of children with oncohematologic pathology. Cefpodoxime proved to be efficient in cases of moderate infectious complications in regard to the respiratory tracts. The oral administration of the drug provided its usage in outpatients. Ceftriaxone had a favourable effect in the treatment of children with more severe processes as a rule at the background of agranulocytosis and a lower immune response often with a tendency to generalization. No side effects of the cephalosporins were observed.

Topics: Administration, Oral; Agranulocytosis; Anemia, Aplastic; Cefpodoxime; Ceftizoxime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Hematologic Neoplasms; Humans; Injections, Intraperitoneal; Opportunistic Infections; Respiratory Tract Infections; Treatment Outcome

The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis.

Topics: Adolescent; Agranulocytosis; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Female; Fever of Unknown Origin; Humans; Infant; Male; Neoplasms; Prospective Studies; Risk Factors

To compare the efficacy and toxicity of single daily dosing of amikacin and ceftriaxone with that of multiple daily dosing of amikacin and ceftazidime for febrile episodes in patients with cancer and granulocytopenia.. A prospective, randomized, unblinded, multicenter trial.. Twenty-one tertiary care or university medical centers.. Six hundred seventy-seven patients with cancer and granulocytopenia (858 febrile episodes).. Random assignment to empiric therapy with a single daily dose of amikacin (20 mg/kg) and ceftriaxone (adults, 30 mg/kg; children, 80 mg/kg) (24-hour group) or with multiple daily doses of amikacin (6.5 mg/kg every 8 hours) and ceftazidime (33 mg/kg every 8 hours) (8-hour group).. Percentage response to each regimen and occurrence of nephrotoxicity and ototoxicity.. Single daily dosing of amikacin and ceftriaxone was as effective as multiple daily dosing of amikacin and ceftazidime (71% compared with 74%; difference, -3%; 95% Cl, -10% to 3%; P > 0.2). Equivalent responses also were noted for each category of infection. Median peak (30 minutes after a 60-minute infusion) serum concentrations of amikacin were higher in the 24-hour group than in the 8-hour group (45.6 compared with 21 micrograms/mL, P < 0.001), whereas trough (preinfusion) levels were lower (0.9 compared with 2 micrograms/mL, P < 0.001). Nephrotoxicity was 3% in the 24-hour group and 2% in the 8-hour group (difference, 1%; Cl, -1% to 4%). Increases in serum creatinine, however, were delayed (P = 0.048) and smaller (P = 0.06) in the 24-hour group than in the 8-hour group and occurred almost exclusively after other nephrotoxic drugs were added. Audiometry was only done in 144 patients (21%). Ototoxicity was 9% in the 24-hour group and 7% in the 8-hour group (difference, 2%; Cl, -7% to 11%; P > 0.2). Further infections developed in 15% and 12% of patients, respectively (difference, 3%; Cl, -2% to 9%). The overall mortality rate was 11% in both treatment groups (difference, 0%; Cl, -5% to 5%).. Single daily dosing of amikacin and ceftriaxone was as effective and no more toxic than multiple daily dosing of amikacin and ceftazidime for the empiric therapy of infection in patients with cancer and granulocytopenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Amikacin; Bacterial Infections; Ceftazidime; Ceftriaxone; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Ear Diseases; Female; Humans; Infant, Newborn; Infections; Kidney Diseases; Male; Middle Aged; Neoplasms; Prospective Studies; Treatment Outcome

The efficacy and safety of the two antibiotic combinations, ceftazidime plus amikacin and ceftriaxone plus amikacin were compared in an open randomized trial. 100 episodes of neutropenia caused by malignant diseases and/or cytostatic drugs were evaluated in 66 males and 34 females with a mean age of 49.4 years. The types of infections treated were: septicemia 38, fever of undetermined origin 26, pneumonia 13, ear, nose and throat infections 11 and others 12. 17 episodes were not evaluable (6 protocol violations, 6 doubtful infections and 5 non-bacterial infections). The overall results were comparable, with a 74% success rate for ceftazidime and a 70% rate for ceftriaxone (criteria of the European Organization for Research and Treatment of Cancer). In the patients with septicemia, the success rate was 64% in the ceftriaxone and 57% in the ceftazidime group. Eight patients died during the treatment, in 5 cases due to infectious complications. There were no differences between the two groups in respect of efficacy or toxicity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Amikacin; Bacterial Infections; Ceftazidime; Ceftriaxone; Drug Therapy, Combination; Female; Fever; Humans; Leukemia; Male; Middle Aged; Neoplasms

Efficacy of the cephalosporin, ceftriaxone, was compared with that of the combination of the aminoglycoside, netilmicin, and the penicillin, azlocillin, in the treatment of febrile episodes in immunocompromised neutropenic children undergoing chemotherapy for neoplastic disease. During 100 separate febrile episodes, 40 strains of bacteria were isolated from the blood of 34 patients and a further 55 strains from other sites. Nine strains (four of which were staphylococci) to both netilmicin and azlocillin. There was no difference in clinical response between the two therapeutic regimens as assessed 4 and 7 days after treatment began. Ceftriaxone had the considerable practical advantages of once daily dosage without a need for blood monitoring. Ceftriaxone would appear to be effective as initial monotherapy in the treatment of bacterial infections in severely neutropenic children.

Topics: Adolescent; Agranulocytosis; Azlocillin; Bacteria; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Netilmicin; Neutropenia; Randomized Controlled Trials as Topic

A prospective study was carried out in 44 patients treated by intensive chemotherapy inducing a prolonged neutropenia (granulocytes less than 0.5.10(9)/l). All the patients were isolated in protected rooms, received a pathogen-free diet and nonabsorbable oral antibiotics. After double-blind randomization, 22 patients received 2 g of Ceftriaxone (Cef) in a daily infusion beginning on the first day of chemotherapy; and 22 patients received 2 g of placebo (P) under the same conditions. Prophylaxis was continued until the neutropenia resolved (granulocytes greater than 0.5.10(9)/l) or until the onset of infectious symptoms. 19 patients in each group developed febrile episodes, occurring significantly later in the Cef group (16.6 days versus 10.6 days in the P group). No Cef-resistant organism was isolated. Finally, the time at which apyrexia was obtained after the beginning of curative antibiotherapy was the same in both groups. The routine intravenous administration of Cef in combination with nonabsorbable antibiotics is a useful approach in reducing the risk of infection in the neutropenic host.

Topics: Adult; Agranulocytosis; Antineoplastic Agents; Bacterial Infections; Ceftriaxone; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Prospective Studies; Risk Factors

In a prospective, randomized study we compared ceftriaxone (active ingredient of Rocephin) plus amikacin, ceftazidime plus amikacin and imipenem/cilastatin in the empiric therapy of febrile granulocytopenic (less than 500/mm3) patients with cancer or aplastic anemia. Of 27 evaluable episodes, 12 were treated with ceftriaxone plus amikacin, 5 with ceftazidime plus amikacin and 10 with imipenem/cilastatin. 56% were culture-positive. Septicemia was the most frequent site of infection and Escherichia coli was the most frequently isolated organism. The efficacy of the three regimens was comparable. One failure occurring in each treatment group was successfully treated with an alternative antibiotic regimen. A second failure in the first treatment group did not respond to the alternative treatment either. No major adverse effects occurred. This study demonstrates that the three regimens are excellent in the empiric therapy of febrile granulocytopenic patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Ceftazidime; Ceftriaxone; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Fever; Humans; Imipenem; Male; Middle Aged; Prospective Studies; Random Allocation; Remission Induction

Prophylactic systemic antibiotherapy with ceftriaxone (CRO) alone was tested in aplastic patients receiving total gut decontamination and treated in protected environment. To enter the study, the patients had to be afebrile when their polymorphonuclear (PMN) count fell under 500/cumm. Seventy eight therapeutic aplasias (after allogeneic or autologous bone marrow transplant conditioning regimens or high dose chemotherapy) form the basis of this report. The median duration of aplasia was 19 D (11-93 D). Forty-three patients received during 51 aplasias one single injection of CRO per day as soon as PMN count was under 500/cumm. In 23 cases (45%) the patients remained afebrile until the end of aplasia. There were 3 Staphylococcus epidermidis bacteremias (6%), 3 bacteriologically documented fevers (6%) and 1 Cryptococcus septicemia. Twenty-nine of these aplasias were part of a randomized study between group A (prophylactic CRO) and group B (non prophylactic CRO: 27 cases). In group A, there were significantly more aplasias without fever (34.5% vs 4%), and less bacteremias (10% vs 48%). Fever appeared later in group A (mean 12.5 D vs 6 D). No death was recorded during the whole study. Thus, in protected environment, prophylactic systemic antibiotherapy could still lessen the risk of bacterial infections. The side effects and the cost of such a procedure appeared to be diminished by a monoantibiotherapy.

Topics: Adolescent; Adult; Agranulocytosis; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Humans; Middle Aged; Neutropenia; Patient Isolation; Premedication

Prophylactic systemic antibiotic therapy with ceftriaxone alone was tested in aplastic patients receiving total gut decontamination and treated in a protected environment. Only patients who were afebrile when their polymorphonuclear (PMN) count fell below 500/cumm were admitted to the study. Seventy-eight episodes of therapeutic aplasia (consecutive to allogeneic or autologous bone marrow transplant conditioning regimens or to high dose chemotherapy) form the basis of this report. The median duration of aplasia was 19 days (range 11-93 days). Twenty patients received, during 22 episodes of aplasia, one single injection of ceftriaxone per day as soon as their PMN count was below 500/mm3. In 13 cases (59%) the patients remained afebrile until the end of aplasia, and no bacteriemia was detected. The second part of the study was randomized between group A (prophylactic ceftriaxone: 29 cases) and group B (no prophylactic ceftriaxone: 27 cases). Patients in group A had significantly more episodes of afebrile aplasia (34.5% vs 4%) and less bacteriemias (10% vs 48%) than those in group B. Also fever developed later in group A (mean: 12.5 vs 6 days). No death was recorded throughout the study. Thus, in a protected environment prophylactic systemic antibiotic therapy could still lessen the risk of bacterial infection. Using one single antibiotic seemed to reduce the side-effects and cost of the prophylactic treatment.

Topics: Adolescent; Adult; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Clinical Trials as Topic; Drug Therapy, Combination; Environment, Controlled; Humans; Middle Aged; Neutropenia; Random Allocation

Topics: Agranulocytosis; Aztreonam; Bacterial Infections; Cefazolin; Ceftriaxone; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Male; Neoplasms

We present a case of a 75-year-old woman with Austrian syndrome: pneumonia, meningitis and endocarditis all due to

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Ceftriaxone; Comorbidity; COVID-19; Echocardiography, Transesophageal; Endocarditis, Bacterial; Female; Humans; Meningitis, Bacterial; Pandemics; Pneumococcal Infections; SARS-CoV-2; Streptococcus pneumoniae; Syndrome

Agranulocytosis from antimicrobial therapy with ceftriaxone is rare. We report a case of agranulocytosis resulting from ceftriaxone noted more than 3 weeks into therapy.. A 72-year-old woman who was started on ceftriaxone for septic arthritis of the left knee 3 weeks before presentation was admitted to the hospital after being found to be neutropenic on outpatient laboratory analysis. Her absolute neutrophil count on admission was 0/μL. The cause of the agranulocytosis was suspected to be ceftriaxone. The drug was stopped, and she was started on granulocyte colony-stimulating factor with gradual resolution of the neutropenia.. Serious adverse effects of ceftriaxone therapy, such as agranulocytosis, must be monitored for, especially in patients who are receiving prolonged therapy or high doses. Once this cause of agranulocytosis is identified, ceftriaxone therapy should be stopped; if the patient is febrile, an infectious disease workup should be performed and antibiotics should be started; and granulocyte colony-stimulating factor should be administered with daily monitoring of the absolute neutrophil count.

Topics: Aged; Agranulocytosis; Ambulatory Care; Anti-Bacterial Agents; Arthritis, Infectious; Ceftriaxone; Female; Granulocyte Colony-Stimulating Factor; Humans

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Bone Marrow; Ceftriaxone; Fatal Outcome; Female; Humans; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Infection; Pulmonary Aspergillosis; Pyelonephritis

Topics: Adult; Agranulocytosis; Ambulatory Care; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Female; Humans; Injections; Leukocyte Count; Neutrophils

The present report describes a very rare case of an aortic homograft valve endocarditis caused by Cardiobacterium hominis. The case was complicated by an agranulocytosis after 3 weeks of antibiotic treatment induced by ceftriaxone. Alternative oral treatment with ciprofloxacin and rifampicin was successful, no surgical intervention was needed and homograft function could be preserved.

Topics: Agranulocytosis; Anti-Bacterial Agents; Aortic Valve; Aortic Valve Insufficiency; Bacteremia; Bioprosthesis; Cardiobacterium; Ceftriaxone; Drug Therapy, Combination; Endocarditis, Bacterial; Follow-Up Studies; Gram-Negative Bacterial Infections; Heart Valve Prosthesis; Humans; Infant, Newborn; Male; Middle Aged; Prosthesis Failure; Recurrence; Reoperation; Transplantation, Homologous

Aerococcus viridans, a catalase-negative gram-positive coccus rarely causing bacteremia, was isolated from blood cultures of a 52-yr-old man under the granulocytopenic condition. The isolate showed the typical characteristics of A. viridans, i.e., tetrad arrangements in gram stain, positive pyrrolidonyl aminopeptidase (PYR) and negative leucine aminopeptidase (LAP) reactions, and no growth at 45 degrees C. The isolate was revealed to be highly resistant to penicillin, erythromycin, clindamycin, and ceftriaxone, although most strains of A. viridans isolated from the previously reported patients were susceptible to penicillin and other commonly used antibiotics. Even though A. viridans is rarely associated with human infections, it could be a potential causative agent of bacteremia, especially in immunocompromised patients.

Topics: Agranulocytosis; Bacteremia; Ceftriaxone; Clindamycin; Drug Resistance, Multiple, Bacterial; Erythromycin; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Penicillins; Streptococcaceae

Topics: Aged; Agranulocytosis; Ceftriaxone; Cephalosporins; Drug Administration Schedule; Endocarditis, Bacterial; Epilepsy, Tonic-Clonic; Humans; Male; Streptococcal Infections; Streptococcus bovis; Time Factors

Administration of broad-spectrum antibiotics as empiric therapy to febrile granulocytopenic patients has become a widely accepted practice. In order to evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily doses as empiric treatment for febrile granulocytopenic children with cancer, a retrospective review (January-December 1996) of all febrile episodes at our institution was carried out. Overall, 101 febrile episodes in 89 granulocytopenic children with cancer were empirically treated with a once-daily ceftriaxone plus amikacin combination. 59/101 (59%) patients had absolute granulocyte count lower than 100/mm3 at entry; 46 (45%) were affected by solid tumors, 16 (15%) by Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow transplantation. The ceftriaxone plus amikacin combination was effective in 72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4). We also evaluated the economic advantages of the ceftriaxone plus amikacin once-daily regimen when compared with another treatment regimen such as ceftazidime plus amikacin requiring three daily doses. Compared with the multiple daily dose regimen of ceftazidime plus amikacin, there is a cost saving of US $11 (17,500 Italian liras) and US $66 (105,000 Italian liras) for both 1-day and 6-day treatments, respectively, by using the single daily dose regimen of ceftriaxone plus amikacin. The potential of ceftriaxone to lower costs in hospitalized patients depends upon its comparable efficacy with other extended-spectrum beta-lactams, in which case it can reduce overall treatment costs because of its once-daily administration schedule.

Topics: Adolescent; Agranulocytosis; Amikacin; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cost Control; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever of Unknown Origin; Humans; Infant; Male; Neoplasms; Retrospective Studies; Treatment Outcome

Topics: Aged; Agranulocytosis; Ceftriaxone; Cephalosporins; Diagnosis, Differential; Endocarditis, Bacterial; Humans; Male; Streptococcal Infections; Streptococcus sanguis

Topics: Adult; Agranulocytosis; Ceftriaxone; Female; Humans; Leukocyte Count; Male; Middle Aged; Neutropenia; Time Factors

For the treatment of febrile episodes in granulocytopenic cancer patients, a combination of bactericidal and intravenously administered broad spectrum agents is recommended. An aminoglycoside plus a beta-lactame (piperacillin, azlocillin or IIIrd generation cephalosporins) are the drugs of first choice in an empiric approach. Because of frequent parenteral interventions (e.g. catheters, cannulations) in thrombopenic patients with multifactorial immunosuppression, we consider the application of once daily drugs, such as ceftriaxone, netilmicin or amikacin. For single dose treatment (1st day two applications), we used ceftriaxone in combination with netilmicin or amikacin as the first approach and retrospectively evaluated 47 patients for efficacy and safety.

Topics: Adult; Agranulocytosis; Amikacin; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Netilmicin; Retrospective Studies

The optimal management of fever in granulocytopenic patients remains controversial. This pilot study investigated the potential value of single daily doses of amikacin administered empirically with ceftriaxone in febrile granulocytopenic patients. None of the patients died as a result of infection or toxicity from the prescribed regimen. Serum concentrations failed to show drug accumulation. Modifications of empirical antimicrobial therapy were made at a similar rate to other conventional regimens. Vancomycin seemed to increase the incidence of nephrotoxicity. Overall, this pilot study suggests that empirical therapy with single daily doses of amikacin plus ceftriaxone is safe and effective and should be further investigated in a larger number of patients.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Bacterial Infections; Ceftriaxone; Drug Administration Schedule; Drug Therapy, Combination; Female; Hearing; Humans; Male; Middle Aged; Pilot Projects; Vancomycin

Lyme disease, now the most common tick-borne illness in the United States, has recently received much media attention, due in part to its potentially serious sequelae in untreated patients. Because a rare patient with late illness may lack antibodies to the etiologic agent, Borrelia burgdorferi, physicians may be tempted to give empiric antibiotics for illnesses that may not be Lyme disease. We have described a patient who, despite negative laboratory evidence for late Lyme disease, was treated for 3 weeks with intravenous ceftriaxone and sustained serious complications, including granulocytopenia, fever, hepatitis, and Clostridium difficile-associated diarrhea. We caution physicians to weight carefully the risks of empiric treatment for ill-defined medical problems, and to recognize the hazards of even "safe" medications.

Topics: Adult; Agranulocytosis; Ceftriaxone; Enterocolitis, Pseudomembranous; Humans; Injections, Intravenous; Lyme Disease; Male; Serologic Tests

The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of the plasma concentrations in vivo and those of the Hill equation the corresponding time course of ER was calculated and by integration with respect to time (0tERdt), an estimate was obtained of the effect on bacteria. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.

Topics: Agranulocytosis; Animals; Cefamandole; Ceftazidime; Ceftriaxone; Cefuroxime; Cephalosporins; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Mice; Protein Binding; Specific Pathogen-Free Organisms

Topics: Agranulocytosis; Cefotaxime; Ceftriaxone; Humans; Neutropenia; Time Factors

In our study ceftriaxone plus amikacin were employed as empirical antibiotic therapy. This antibiotic treatment allows for a once daily administration and has a broad spectrum of activity. 21 febrile episodes were treated with an antibiotic regimen of ceftriaxone 50 mg/kg/day and amikacin 30-35 mg/kg/day i.v. An earlier pilot study was carried out in which 47 febrile episodes were treated with an antibiotic regimen of ceftriaxone 80-100 mg/kg/day i.v. and amikacin 30-35 mg/kg/day i.v. in a single dose. The overall response rate was 76% (16/21) and 79% (37/47) for the pilot study. During the treatment no side effects were observed and aminoglycoside related toxicity did not occur. In conclusion, this empiric antibiotic therapy gives a high response rate and allows for a single daily administration.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Humans; Middle Aged

The effects of monocytopenia and granulocytopenia on the proliferation of Klebsiella pneumoniae and the efficacy of treatment with ceftriaxone were studied in an experimental lung infection in mice. Treatment with etoposide led to monocytopenia, and cyclophosphamide to granulocytopenia and monocytopenia. Both drugs gave a decrease in the number of alveolar macrophages during the infection and a diminished influx of granulocytes into the alveolar space. The mice treated with etoposide did not differ from controls with respect to either the proliferation of Kl. pneumoniae during the infection or the antibiotic efficacy of ceftriaxone. In cyclophosphamide-treated mice the proliferation rate of Kl. pneumoniae was higher than that in the control mice and a higher dose of ceftriaxone was needed to reduce the number of bacteria to the level in the controls. From these findings it is concluded that granulocytes play an important role in the numerical reduction of Kl. pneumoniae and that monocytes make no contribution to infection control in this model.

Topics: Agranulocytosis; Animals; Ceftriaxone; Cyclophosphamide; Etoposide; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases; Mice; Monocytes

Topics: Aged; Aged, 80 and over; Agranulocytosis; Ceftriaxone; Female; Granulocytes; Hematopoiesis; Humans

Topics: Adult; Agranulocytosis; Ceftriaxone; Humans; Male; Neutropenia

A 75-year-old man developed acute transient agranulocytosis. Hematologic data and course were suggestive of a toxic etiology. The patient had been admitted for pneumococcal septicemia and a polymicrobial abscess of the soft tissues of the left leg. At the time of diagnosis of the agranulocytosis, he had received 36 g ceftriaxone. The agranulocytosis resolved following discontinuation of ceftriaxone. This drug was, in all likeliness, responsible for the hematologic disorder. Renal failure occurred concomitantly with the agranulocytosis. Other similar cases have been reported. In view of these data, blood counts should be monitored in patients receiving prolonged courses of ceftriaxone.

Topics: Abscess; Acute Kidney Injury; Aged; Agranulocytosis; Ceftriaxone; Humans; Long-Term Care; Male; Pneumococcal Infections; Sepsis

Ceftriaxone (CFX) is a new third-generation cephalosporin with interesting characteristics as regards both its antibacterial spectrum and kinetics which make it potentially useful in the empiric treatment of infections in neutropenic cancer patients. However, since its kinetic characteristics in children with leukemia are not known and its pharmacokinetics are reported to be altered in such patients, we studied ceftriaxone's activity in ten leukemic children with fever and neutropenia. Our findings seem to be confirm the potential efficacy of the drug also in this particular type of patient.

Topics: Agranulocytosis; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Fever; Half-Life; Humans; Injections, Intravenous; Kinetics; Leukemia, Lymphoid

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With beta-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas beta-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and beta-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.

Topics: Agranulocytosis; Aminoglycosides; Animals; Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Female; Gentamicins; Humans; Metabolic Clearance Rate; Mice; Netilmicin; Peritonitis; Pseudomonas Infections; Ticarcillin

Topics: Aged; Agranulocytosis; Cefotaxime; Ceftriaxone; Female; Humans; Neutropenia