ro13-9904 and Neoplasms

Stomatococcus mucilaginosus, a normal inhabitant of the human oral cavity and upper respiratory tract, can cause fatal sepsis and meningitis in neutropenic patients. We identified eight cases of bacteremia due to S. mucilaginosus in children with cancer, of whom five developed complications despite receiving appropriate antibiotics. At the time cultures were positive, seven patients had profound neutropenia (< 100 neutrophils and band forms/mm3) and four had mucositis; five had central venous catheters. In two cases, there was unequivocal evidence of catheter-related sepsis. Bacteremia was eradicated in all patients within 48 hours after initiation of antibiotics. Despite prompt instigation of effective antibiotic therapy, the complication rates in this series were high: septic shock (50%), pneumonia (50%), dermatologic manifestations (38%), altered neurological status (25%), meningitis (13%), and adult respiratory distress syndrome (13%). No fatalities were attributable to S. mucilaginosus infection. These cases illustrate the virulence of S. mucilaginosus organisms in neutropenic children and suggest a substantial risk of sequelae even when adequate antibiotic therapy is given.

Topics: Adolescent; Bacteremia; Ceftazidime; Ceftriaxone; Child; Child, Preschool; Female; Gram-Positive Bacterial Infections; Humans; Male; Meningitis, Bacterial; Micrococcaceae; Neoplasms; Neutropenia; Pneumonia; Respiratory Distress Syndrome; Shock, Septic; Skin Diseases; Vancomycin

In human subjects, ceftriaxone exhibits an exceptionally long elimination half-life (5.8 to 8.7 hours) and a small degree of nonlinearity in its pharmacokinetics which can be ignored in its clinical applications. Thirty-three to 67 percent of a dose is excreted in the urine as unchanged drug, and the remainder is secreted in the bile and ultimately is found in the feces as microbiologically inactive compounds. Ceftriaxone is rapidly and completely absorbed following intramuscular administration. Multiple dosing of ceftriaxone with doses ranging from 0.5 to 2 g at 12- or 24-hour intervals by intravenous and intramuscular routes resulted in 15 to 36 percent accumulation of ceftriaxone in plasma and no change in its elimination half-life. The volume of distribution and the plasma clearance of ceftriaxone in pediatric patients were threefold greater than those in adults, and ceftriaxone penetrated the inflamed meninges of infants and children with bacterial meningitis. Small changes in the pharmacokinetics of ceftriaxone in elderly subjects or patients with renal or hepatic dysfunction are such that dose adjustments should not be necessary with a ceftriaxone dosage up to 2 g per day. Ceftriaxone was not removed to any significant extent from plasma by hemodialysis. In a small percentage of patients, on dialysis, the elimination rate of ceftriaxone was significantly reduced, suggesting that plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary.

Topics: Adolescent; Adult; Age Factors; Aged; Blister; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Injections, Intravenous; Kidney; Kidney Diseases; Kinetics; Middle Aged; Milk, Human; Neoplasms; Placenta; Pregnancy

Pediatric oncology patients with fever, even when not neutropenic, are known to be at an increased risk of bloodstream infections. However, there are no standard guidelines for management of fever in non-neutropenic patients, resulting in variability in practice across institutions.. We retrospectively analyzed the clinical characteristics, management, and outcome of all febrile non-neutropenic episodes in pediatric oncology patients at a single institution over the two-year period 2011-2012, to identify predictors of bloodstream infections. We assessed the efficacy of a uniform approach to outpatient management of a defined subset of patients at low risk of invasive infections.. A total of 254 episodes in 83 patients were identified. All patients had implanted central venous catheters (port). Sixty-two episodes (24%) were triaged as high-risk and admitted for inpatient management; five (8%) had positive blood cultures. The remaining 192 episodes were triaged as low risk and managed with once daily outpatient intravenous ceftriaxone; three (1.6%) were associated with bacteremia, and 10% required eventual inpatient management. Of all the factors analyzed, only signs of sepsis (lethargy, chills, hypotension) were associated with positive bloodstream infection.. Treatment of a defined subset of patients with outpatient intravenous ceftriaxone was safe and effective. Signs of sepsis were the only factor significantly associated with bloodstream infection. This study provides a baseline for future prospective studies assessing the safety of withholding antibiotics in this subset of patients.

Topics: Bacteremia; Ceftriaxone; Child; Child, Preschool; Female; Fever; Follow-Up Studies; Humans; Infant; Male; Neoplasms; Retrospective Studies; Risk Factors

Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia (LRFN) as there is insufficient data regarding its equivalence as compared with parenteral therapy.. This is a single institutional, randomized control trial in pediatric LRFN aged 2 to 15 years, in which 123 episodes in 88 patients were randomized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/kg 8 hourly or outpatient intravenous (IV) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures.. Out of 119 evaluable episodes, one-third were leukemia patients in maintenance and rest were solid tumors. Success was achieved in 55/61 (90.16%) and 54/58 (93.1%) in oral and IV arms, respectively, (P=0.56). There were 3 hospitalizations but no mortality. Median days to resolution of fever, absolute neutrophil count >500/mm(3) and antibiotic use were 3, 5, and 6 days in both arms. There were 5 blood culture isolates (3 gram-positive and 2 gram-negative bacteria). Failure of outpatient therapy was associated with perianal infections, bacteremia, febrile neutropenia onset before day 9 of chemotherapy in solid tumors and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy for rhabdomyosarcoma. All gram-positive isolates were successes, whereas both gram-negative isolates were failures. Diarrhea in IV arm and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy in the oral arm predicted failure in subgroup analysis.. Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice.

Topics: Administration, Oral; Adolescent; Ambulatory Care; Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Ceftriaxone; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Male; Neoplasms; Neutropenia; Ofloxacin; Treatment Outcome

Patients with low-risk neutropenic fever as defined by the Multinational Association of Supportive Care in Cancer (MASCC) score might benefit from ambulatory treatment. Optimal management remains to be clearly defined, and new oral antibiotics need to be evaluated in this setting.. Cancer patients with febrile neutropenia and a favorable MASCC score were randomized between oral moxifloxacin and intravenous ceftriaxone. All were fit for early hospital discharge. The global success rate was related to the efficacy of monotherapy, as well as to the success of ambulatory monitoring.. The trial was closed prematurely because of low accrual. Ninety-six patients were included (47 in the ceftriaxone arm and 49 in the moxifloxacin arm). A total of 65% were women, 30.2% had lymphoma, 34.4% had metastatic, and 35.4% had non-metastatic solid tumors. The success rates of home antibiotics were 73.9% and 79.2% for ceftriaxone and moxifloxacin, respectively. Seven patients were not discharged, and 14 required re-hospitalization. There were 17% of microbiologically documented infections that were, in most cases, susceptible to oral monotherapy.. These results suggest that MASCC is a valid and useful tool to select patients for ambulatory treatments and that oral moxifloxacin monotherapy is safe and effective for the outpatient treatment of cancer patients with low-risk neutropenic fever.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Aza Compounds; Ceftriaxone; Female; Fever; Fluoroquinolones; Humans; Infusions, Intravenous; Male; Middle Aged; Moxifloxacin; Neoplasms; Neutropenia; Patient Discharge; Quinolines; Risk Factors; Time Factors

Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care.. Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control). Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization, and cost between both groups.. A prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated on an outpatient basis. We found a statistically significant difference between the duration of hospitalization of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P < 0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications.. We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization.

Topics: Ambulatory Care; Amikacin; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Costs and Cost Analysis; Female; Humans; Injections, Intravenous; Length of Stay; Male; Neoplasms; Neutropenia; Patient Discharge; Prospective Studies; Risk Factors; Sepsis; Time Factors

Broad-spectrum beta-lactam is the standard therapy for febrile neutropenia (FN) in cancer patients. The aim of our study was to evaluate the treatment of FN by a once-daily administration of ceftriaxone (CFX) alone.. From Jan. 1, 1997 to Dec. 31, 2001 we prospectively analyzed 100 episodes of FN in 94 patients. Inclusion criteria were: fever > or = 38.5 degrees C, neutrophil count (NC) <500/microl, presumed short duration (<7 days), and no antimicrobial treatment within the preceding 72 h. Treatment consisted of 2 g daily intravenous CFX alone until NC>500. Success criteria were: afebrile within 48 hours under CFX alone and without secondary infection.. Twenty-seven episodes occurred in patients with performance status (PS)>2. The median duration of neutropenia was 3.5 days (range 1-22). Etiology of fever was: 75 of unknown origin (FUO), 6 clinically defined (CDI), and 19 microbiologically documented (MDI). Median CFX treatment duration was 5 days. Successful response was obtained in 87% of cases; no deaths occurred. Treatment efficacy differed between FUO, CDI, and MDI with, respectively, 92.0, 83.3, and 68.4% success rates (p=0.042). Treatment failure was mostly observed in patients with PS > or = 2 (p=0.0001). Among the 13 failures, 4 resolved in less than 4 days with CFX alone and 9 required additional or modified antimicrobial treatment.. Considering the marked practical advantages of CFX alone (well-tolerated treatment with minimum side effects, once-daily administration, low cost, and high response rates), this single-agent regimen appears to be a valuable option in treatment of FN in patients with solid tumors.

Topics: Adult; Aged; Aged, 80 and over; Ceftriaxone; Drug Therapy, Combination; Female; Humans; Infections; Injections, Intravenous; Male; Middle Aged; Neoplasms; Neutropenia

Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. The purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin.. One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospective, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adverse events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out.. There were 176 evaluable patient-episodes with 51.1% in the single-daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin group. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gram-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56). Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicity was not evaluable.. The once-daily regime of ceftriaxone plus amikacin was as effective as the 'standard' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health resources and in centres with a low prevalence of P. aeruginosa.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteremia; Ceftazidime; Ceftriaxone; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Humans; Logistic Models; Male; Multivariate Analysis; Neoplasms; Neutropenia; Prospective Studies; Statistics, Nonparametric

Infections are one of the major complications in children undergoing chemotherapy. Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients (solid tumors and stage I/II lymphomas). The same drugs may be used in an outpatient setting, decreasing costs and the risk of nosocomial infections.. Low-risk patients (N = 70) with episodes of fever and neutropenia (N = 116) were randomized to receive either oral ciprofloxacin or intravenous ceftriaxone as outpatients. Only one patient had a central venous catheter.. Episodes of fever and neutropenia were classified as fever of unknown origin (41% vs. 32%) or clinically documented infection (56% vs. 63%) in the ciprofloxacin and ceftriaxone groups, respectively. Most of these infections were of upper respiratory tract, skin, or gastrointestinal origin. The mean duration of neutropenia was 5 vs. 6 days. Fever persisted for 1-9 days (mean 2 vs. 3 days). Therapy was successful with no modifications in 83% vs. 75% of the episodes. Patients were admitted in 7% vs. 4% of the episodes. No bone or joint side effects were seen in either group. All patients survived.. Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma (low-risk patients).

Topics: Administration, Oral; Adolescent; Adult; Ambulatory Care; Anti-Infective Agents; Antineoplastic Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Ciprofloxacin; Fever; Humans; Neoplasms; Neutropenia; Prospective Studies; Risk Factors

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Fever; Humans; Infant; Infusions, Intravenous; Middle Aged; Neoplasms; Neutropenia; Outpatients; Prospective Studies; Treatment Outcome

Hospitalization and empirical broad-spectrum, intravenous antibiotics are the standard treatment for febrile cancer patients. Recent evidence supports the suggestion that febrile episodes in a low-risk population can be managed successfully in an outpatient setting, but the optimal drug regimen is unknown. In a prospective randomized clinical trial we compared ciprofloxacin 750 mg p.o. twice a day with ceftriaxone 2 g i.v. as a single daily dose for the empiric domiciliary treatment of febrile episodes in low-risk neutropenic and nonneutropenic cancer patients. A total of 173 patients, accounting for 183 febrile episodes, were enrolled in the study. Overall, successful outcomes were recorded for 76 of 93 (82%) febrile episodes in patients who were randomized to the oral regimen and for 68 of 90 (75%) febrile episodes in patients randomized to the i.v. regimen: this difference was not statistically significant. The success rate was similar in all subgroups of patients: neutropenic and nonneutropenic, with documented infection and with fever of unknown origin. There were 3 deaths in the group of patients treated with the parenteral regimen, and two of these were related to treatment failure. Both treatments were well tolerated, and the cost of the oral regimen was lower. This prospective study suggests that domiciliary antibiotic empiric monotherapy is feasible in febrile nonneutropenic or low-risk neutropenic outpatients in whom a bacterial infection is suspected, and that either an oral or a parenteral regimen can be used. A number of factors may influence the choice between an orally and an i.v.-administered antibiotic, but owing to the easier administration and lower cost, the oral regimen seems to be preferable.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Bacterial Infections; Ceftriaxone; Cephalosporins; Ciprofloxacin; Female; Fever; Humans; Infusions, Parenteral; Male; Middle Aged; Neoplasms; Neutropenia; Outpatients; Prospective Studies; Treatment Outcome

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

The aim of this study was to determine the efficacy of antibiotic prophylaxis in percutaneous endoscopic gastrostomy (PEG).. An open prospective, randomised, multicenter study was conducted in 141 patients; 72 received ceftriaxone 1 g i.v. 30 min preintervention, and 69 received no study medication. A standardized protocol was followed for PEG preparation, insertion, and aftercare; all patients received a 15-Fr gastrostomy tube. Follow-up of local and systemic infection and clinical course was continued to postintervention day 10. An aggregate erythema and exudation score >3 or the presence of pus was taken as indicative of peristomal infection. The pharmacoeconomics of antibiotic use were also examined.. In no-prophylaxis patients, wound infection rates were 25% on day 4 and 26.4% on day 10, versus 10.1% (p = 0.03) and 14.5% (p = 0.10), respectively, in prophylaxis patients. Results were disproportionally better in tumor patients: systemic infection rates were 16.7% versus 5.8% in no-prophylaxis versus prophylaxis patients (p = 0.045), and overall infection rates 38.9% versus 17.4%, respectively (p = 0.046). Pneumonia was more frequent in patients with underlying neurological disease. Antibiotic costs were the same in both groups (p = 0.792).. Single dose ceftriaxone 1 g is an effective prophylaxis against local and systemic infection after PEG.

Topics: Aged; Antibiotic Prophylaxis; Bacteremia; Ceftriaxone; Cephalosporins; Drug Costs; Economics, Pharmaceutical; Enteral Nutrition; Erythema; Exudates and Transudates; Female; Follow-Up Studies; Gastroscopy; Gastrostomy; Humans; Male; Neoplasms; Nervous System Diseases; Pneumonia; Prospective Studies; Sepsis; Suppuration; Surgical Wound Infection

A study was performed in low-risk cancer patients with chemotherapy-induced febrile neutropenia to determine the safety and efficacy of ceftriaxone given in an outpatient setting. A total of 126 episodes of febrile neutropenia in 120 clinically stable outpatients were treated with intravenous ceftriaxone alone (n=100) or in combination with other antibiotics (n=26). The mean neutrophil count was 460/mm3; severe neutropenia (< 100/mm3) was observed in 18 episodes. The initial treatment with ceftriaxone (alone or in combination) was successful in 99 episodes (78%). Ninety-five episodes (76%) were successfully treated in an outpatient setting only; admission to hospital was necessary in 31 episodes (24%), but no infection-related death was observed. Ceftriaxone seems to be safe and effective for outpatient therapy of patients with low-risk febrile neutropenia.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Antibiotic Prophylaxis; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Hematologic Neoplasms; Humans; Infant; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies

The combination of ceftazidime plus aminoglycoside is widely used for the treatment of febrile neutropenic patients but requires multiple daily administration. Because the frequency of Pseudomonas aeruginosa is low in many centers, there is a rationale to test other antibiotic regimens that provide appropriate antibacterial coverage with the advantage of reduced dosing frequency, such as once daily ceftriaxone plus amikacin.. Febrile neutropenic children with leukemia, lymphoma or solid tumors after chemotherapy were included in an open, prospective, randomized, multinational study comparing once daily ceftriaxone plus amikacin vs. 8-hourly ceftazidime and amikacin. The response to antimicrobial therapy was defined as complete response, improvement or failure. Assessment of adverse events was supplemented by specific definitions of nephrotoxicity, ototoxicity, hepatotoxicity and hypokalemia. Costs were estimated from published values of acquisition costs, delivery costs and hospitalization costs.. Efficacy was evaluable in 364 of 468 episodes in 265 children. Response rates in ceftriaxone and amikacin vs. ceftazidime and amikacin-treated episodes were 119 of 181 (66%) vs. 121 of 183 (66%), 7 of 181 (4%) vs. 9 of 183 (5%) and 55 of 181 (30%) vs. 53 of 181 (29%) for complete response, improvement and failure, respectively. Safety profiles were similar with both treatment regimens. The acquisition and administration costs were lower for the ceftriaxone and amikacin regimen.. A once daily regimen of ceftriaxone and amikacin is as safe and clinically effective as that of three times daily ceftazidime and amikacin for the treatment of febrile neutropenic children with cancer and is more cost-effective. The once daily regimen of ceftriaxone and amikacin is suitable for outpatient treatment.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Fever; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant; Leukemia; Lymphoma; Male; Microbial Sensitivity Tests; Neoplasms; Neutropenia

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

Isepamicin is a new aminoglycoside with in-vitro activity superior to amikacin. It is a poor substrate for the 6'-aminoacetyltransferase-I enzyme which inactivates amikacin and therefore organisms possessing this enzyme are not resistant to isepamicin. The aim of this study was to compare the efficacy and safety of co-administration of isepamicin once daily plus ceftriaxone to amikacin twice daily plus ceftriaxone to amikacin twice daily plus ceftriaxone in febrile neutropenic cancer patients. Febrile episodes in 235 patients (156 in isepamicin group and 79 in amikacin group) were treated in this study. They occurred in 218 different patients. Fifteen patients were enrolled twice and one three times. Response rates to the two treatment regimens for microbiologically documented episodes, clinically documented episodes and further unexplained fever were similar. Tolerance of the treatment regimens, as measured by serum creatinine levels, hypoaccousia and cutaneous allergy was also similar in both treatment groups. In conclusion, isepamicin given once daily when combined with ceftriaxone in the treatment of febrile episodes in neutropenic cancer patients was as effective and no more toxic than amikacin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Bone Marrow Transplantation; Ceftriaxone; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Gentamicins; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Superinfection

The feasibility and efficacy of a once daily antibiotic regimen were assessed in children with malignant tumours. Over a 44 month period, 296 febrile episodes were treated with a regimen of once daily ceftriaxone-amikacin (and teicoplanin or vancomycin if the patient had a central line). The treatment was successful in 272 (92%) episodes without modification of the antibiotic regimen, and only one patient died of uncontrolled sepsis. A once daily antibiotic regimen is therefore feasible and worthwhile in the treatment of febrile episodes in children with cancer.

Topics: Adolescent; Adult; Amikacin; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Feasibility Studies; Humans; Infant; Neoplasms; Teicoplanin; Vancomycin

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

Three hundred and twenty patients were enrolled in a prospective randomized trial comparing cefoperazone, ceftizoxime and ceftriaxone for initial therapy of infectious episodes in cancer patients. Patients with neutropenia were excluded. In 286 evaluable episodes, the response rates associated with the three agents were 77% for cefoperazone, 70% for ceftizoxime and 72% for ceftriaxone, with no statistically significant differences between the three treatment groups. The overall response rate for all episodes of pneumonia (64%) was significantly lower than the response rate for all other infections (81%; p = 0.002), and the mortality associated with pneumonia (9%) was higher than that associated with all other episodes (2%; p = 0.01). Patients with infections due to gram-negative organisms responded well to all three agents, whereas patients with gram-positive infections responded more favorably to cefoperazone. Two different schedules of ceftriaxone were used. The clinical response did not differ significantly between patients receiving ceftriaxone once daily and those receiving it twice daily. The incidence of superinfection and relapse was extremely low and all three agents were well tolerated. It is concluded that extended spectrum cephalosporins are effective as single agents for the treatment of infections in cancer patients with adequate neutrophil counts.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Cefoperazone; Ceftizoxime; Ceftriaxone; Costs and Cost Analysis; Drug Administration Schedule; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Neoplasms; Pneumonia; Prospective Studies; Remission Induction

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

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

Cancer patients are prescribed antibiotics, such as macrolides and lactamides, for infection treatment. However, the effect of these antibiotics on NLRP3 activation remains largely unknown.. Lung cancer (A549) and prostate cancer (PC3) cell lines were primed with lipopolysaccharide (LPS) to activate NLRP3 transcription. Cells were then treated with azithromycin (Az) or ceftriaxone (Cf). NLRP3 activation was analyzed by qPCR, Western blot, and ELISA. Cell growth and viability were assessed by real-time cell analysis and Annexin V expression. Levels of 41 cytokines were also analyzed using a multiplex assay.. LPS-Az activated transcription of. Our data suggest that Cf could suppress LPS induced NLRP3, which should be considered when selecting antibiotics for cancer treatment. In contrast, the effect of Az on LPS primed NLRP3 and the inflammatory cytokines production appears to depend on the cancer cell origin. Therefore, these data indicate that considerations are required when selecting Az for the treatment of cancer patients.

Topics: Azithromycin; Ceftriaxone; Cell Line, Tumor; Cytokines; Humans; Inflammasomes; Interleukin-1beta; Lipopolysaccharides; Neoplasms; NLR Family, Pyrin Domain-Containing 3 Protein

There are a limited number of studies that address non-neutropenic fever episodes in children with cancer, and no standard approach exists.. We opt to retrospectively analyze the efficacy of the current clinical approach for management of non-neutropenic fever episodes and the associated risk factors among children with cancer at the Princess Noorah Oncology Center from May 2016 through December 2017.. A total of 480 non-neutropenic fever episodes were identified in 131 children, of which 62 episodes were triaged as high-risk non-neutropenic fever and 418 as low-risk non-neutropenic fever. Of those 480 non-neutropenic fever, 361 episodes (75.2%) were associated with the presence of central venous catheters. The overall failure rate of ceftriaxone mono-therapy was observed in 75.6% (11.7% in high-risk non-neutropenic fever with a mean C-reactive protein level of 21.1 (±23.2) mmol/L and 63.9% in low-risk non-neutropenic fever with a mean C-reactive protein level of 17.6 (±53.9) mmol/L). The overall bacteremia rate was 14.4%. The type of organisms isolated was mainly high-risk organisms in 59 non-neutropenic fever episodes (85.5%), OR 1.78 (95% CI: 0.45-7.04) p = 0.41. Of note, all bacteremia were associated with the presence of central venous catheter (100%). Of all the examined risk factors of outpatient treatment failure in low-risk non-neutropenic fever, only prolonged fever of more than three days were significantly associated with bacteremia OR 8.107 [95% CI: 1.744-37.691], p = 0.008. Noteworthy is that almost 43% of non-neutropenic fever episodes were associated with respiratory symptoms. This study provides a baseline for future prospective research assessing the pattern of non-neutropenic fever by focusing on associated risk factors.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; C-Reactive Protein; Catheter-Related Infections; Ceftriaxone; Central Venous Catheters; Child; Child, Preschool; Disease Management; Female; Fever; Humans; Infant; Infant, Newborn; Male; Neoplasms; Neutropenia; Respiration Disorders; Retrospective Studies; Risk Factors

Topics: Age Factors; Aged; Aged, 80 and over; Antiviral Agents; Azithromycin; Betacoronavirus; Ceftriaxone; Cobicistat; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Darunavir; Drug Therapy, Combination; Female; HIV Protease Inhibitors; Humans; Hydroxychloroquine; Italy; Lopinavir; Male; Methylprednisolone; Middle Aged; Neoplasms; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2

To identify clinical and microbiological characteristics of Shigella infections among cancer patients.. The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised medical records from December 2011 to November 2013 which were reviewed to identify persons with laboratory-confirmed Shigella infections. Demographic information, clinical history, seasonal variation, microbiological details, treatment given, and outcomes in term of symptoms resolution and mortality at two weeks were noted.. Shigella infection was diagnosed in 45 cancer patients. The mean age of the patients was 36.02±19.30 years (range: 1-64 years), with 35(78%) patients being >18 years of age. Overall, 16(35.5%) patients had presented during winter months and 40(89%) presented as emergencies. Diarrhoea was present in 44(98%) patients and among them 20(45%) had dysentery whereas 28(64%) had fever and 21(47%) had abdominal pain. Of the total 45 cases, 41(91%) had isolates from stool. Besides, 39(87%) Shigella isolates were further speciated and Shigella flexneri was the most commonly isolated serotype in 25(64.1%). Overall, 42(93%) strains were sensitive to cefixime and ceftriaxone. Mean duration of symptoms resolution was 3.92±1.51 days (range: 1-10 days). No mortality was noted at 2 weeks.. Shigella flexneri was the most common serotype isolated. Majority of the isolates were sensitive to 3rd generation cephalosporins (cefixime/ceftriaxone).

Topics: Adolescent; Adult; Anti-Bacterial Agents; Cefixime; Ceftriaxone; Child; Child, Preschool; Comorbidity; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Pakistan; Retrospective Studies; Shigella flexneri; Young Adult

Febrile neutropenia (FN) is a severe chemotherapy side effect. Hospitalization is recommended for FN episode of high-risk (HR) of complications. Management of FN at lower risk of complications remains unclear.. This is a prospective observation study in patients with solid tumors admitted to the emergency department FN. Collected data included demographics, clinical, biological, therapeutic costs, MASCC score and complications.. Hundred and thirty-seven consecutive FN were recorded in 128 patients. Twenty-six FN (19%) were managed at home (all of them had a MASCC score ≥ 21); 111 (81%) were treated at hospital of which 37 NF were at HR of complications based on clinical and biological parameters (all of them had a MASCC score < 21) and for 74 of them the admission could be discussed (MASCC < 20 or ≥ 20). This group of patients was considerate with intermediate risk (IR). All IR patients were treated with the same antibiotics than outpatients, i.e. ceftriaxone in 36 cases (49%) or amoxicillin/clavulanic acid and ciprofloxacin in 38 cases (51%). For these 74 cases, any severe complication was recorded. Antibiotics were adapted for only 12% of these patients according to bacteriology results.. This study showed the limits of the MASCC score. We did not observe any severe complications in patients admitted to the hospital according to clinical and biological parameters and with the high risk score MASCC. This study had some methodological bias but it allowed us to estimate the cost of the different ways of management and the difficulties to decide the hospitalization in FN.

Topics: Adult; Aged; Ambulatory Care; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antineoplastic Agents; Cancer Care Facilities; Ceftriaxone; Ciprofloxacin; Emergency Service, Hospital; Febrile Neutropenia; Female; France; Hospitalization; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Assessment; Young Adult

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded new insight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the 'ground state', remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation, we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer.

Topics: Animals; Cell Survival; Cells, Cultured; Mice; Molecular Structure; Neoplasms; Neurons; Pharmaceutical Preparations; Sensitivity and Specificity; Stem Cells

Topics: Ambulatory Care; Amikacin; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Costs and Cost Analysis; Female; Humans; Injections, Intravenous; Length of Stay; Male; Monitoring, Physiologic; Neoplasms; Neutropenia; Patient Discharge; Prospective Studies; Risk Factors; Safety Management; Sepsis; Time Factors

Topics: Anti-Bacterial Agents; Argentina; Ceftriaxone; Child; Ciprofloxacin; Humans; Neoplasms; Neutropenia; Outpatients; Randomized Controlled Trials as Topic; Research Design

Topics: Anti-Infective Agents; Ceftriaxone; Cephalosporins; Child; Ciprofloxacin; Fever; Humans; Neoplasms; Neutropenia; Risk 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

To evaluate the pharmacokinetics of once daily (OD) gentamicin and its effectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer.. 59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count < 0.5 x 10(9)/l) after chemotherapy.. Over one year, 113 febrile neutropenic episodes were treated empirically with an OD antibiotic regimen of ceftriaxone (80 mg/kg; maximum 4 g) and gentamicin (7 mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48 hours.. 86 of the 113 episodes settled with the first line antibiotic regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear.. OD gentamicin can be used safely and effectively to treat febrile neutropenia in children with cancer. When used for a short period (< 5 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.

Topics: Adolescent; Ceftriaxone; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Gentamicins; Humans; Infant; Male; Neoplasms; Neutropenia; Prospective Studies

Topics: Adolescent; Adult; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Ceftriaxone; Child; Child, Preschool; Drug Therapy, Combination; Fever of Unknown Origin; Humans; Infant; Neoplasms; Neutropenia; Teicoplanin

Febrile neutropenic children with cancer were eligible for outpatient management with intravenous ceftriaxone therapy if they displayed selected low-risk criteria. Nineteen children were enrolled. All patients had sterile blood cultures, and only one of them was hospitalized because of persistent fever. This pilot study suggests that selected children with febrile neutropenia might be successfully managed without hospitalization.

Topics: Adolescent; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Female; Fever of Unknown Origin; Humans; Infant; Infusions, Intravenous; Leukocyte Count; Male; Neoplasms; Neutropenia; Neutrophils; Platelet Count; Treatment Outcome

Topics: Bacterial Infections; Ceftriaxone; Fever; Neoplasms; Neutropenia; Retrospective Studies; Risk Factors

Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile neutropenic cancer patients. We noted in a previous study that response to empiric therapy was related more to disease classification (solid tumors vs. leukemia) than to the regimen chosen. In the present study we based empiric monotherapy on the underlying disease in treating 240 episodes of fever and neutropenia in 145 children. Patients with leukemia or Stage III/IV non-Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin, whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk group) received ceftriaxone. The regimens were modified in 15% of lower risk and 45% of higher risk episodes. Overall successful outcomes were obtained in 93.2% of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes. The two groups differed significantly in duration of neutropenia, frequency of positive blood cultures and superinfection and the need for modification of the monotherapy (P < 0.05). Empiric monotherapy based on primary disease appears to be safe and effective for febrile neutropenic children with cancer at our Brazilian institution. Further studies will be needed before these findings can be generalized to patient populations in other settings.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Neoplasms; Neutropenia

Once-a-day ceftriaxone and amikacin was administered in case of fever to 46 neutropenic patients attending day hospital for hematologic malignancies. All patients were admitted to a short-term ward for infective complications, but were discharged in the event of prompt disappearance of fever and of clinical signs of infection continuing their therapy either by daily reporting to the hospital, or at home. Response to the initial empiric therapy was obtained in 37 cases (76%). Twenty-four patients who promptly responded to therapy completed their treatment on an outpatient basis, their mean number of days of hospitalization being reduced to 4.6 versus a mean of 9.6 days in the overall patient population being considered. Since the outpatient treatment accounted for 21% of the antibiotic therapy administered, the above treatment may result in cost containment and better quality of life for patients, provided that these data are confirmed by prospective randomized studies.

Topics: Adolescent; Adult; Aged; Amikacin; Antineoplastic Combined Chemotherapy Protocols; Ceftriaxone; Day Care, Medical; Drug Therapy, Combination; Female; Fever; Hematologic Diseases; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Opportunistic Infections; Pilot Projects

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

Topics: Bacterial Infections; Cefoperazone; Ceftizoxime; Ceftriaxone; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Neoplasms

Pharmacological studies of ceftriaxone, a new semisynthetic cephalosporin, were conducted in 35 cancer patients. This antibiotic was administered in a variety of doses and schedules with no observed toxicity. Intramuscular administration of 500 mg of ceftriaxone to seven patients produced mean peak serum concentrations of 32.9 mug/ml 2.0 h after administration. The terminal serum half-life was 10.9 h. Intravenous infusion of 500 mg of ceftriaxone over 5 min to the same group of seven patients produced a mean peak concentration of the drug in serum of 83 mug/ml at the end of administration which decreased to 16.8 mug/ml at 8 h. A dose of 1 g of ceftriaxone given in identical fashion to the same group of seven patients produced mean peak concentrations in serum of 130 mug/ml at the end of administration and 17.3 mug/ml at 12 h. The mean percentages of drug recovered in urine 12 h after single intravenous doses of 500 mg and 1 g were 30 and 20%, respectively. A 1-g dose of ceftriaxone was administered every 8 h to 10 patients, and a 2-g dose was administered every 12 hours to 9 patients. Drug concentrations in serum were measured for each patient after drug administration on day 1, day 3 or 4, and day 7 or 8. The 1-g dose produced an observed mean peak concentration of 154 mug/ml and a mean terminal-phase half-life of 5.6 h on day 3 or 4. The 2-g dose produced a mean peak concentration in serum of 262 mug/ml and a terminal-phase serum half-life of 6.3 h on day 3 or 4. Continuous infusion studies were performed in nine neutropenic patients for up to 8 days by using a loading dose of 1 g over 30 min, followed by 2 g every 8 h. Mean concentrations in serum were maintained at about 135 mug/ml during the infusion period.

Topics: Bacterial Infections; Cefotaxime; Ceftriaxone; Female; Half-Life; Humans; Kinetics; Male; Neoplasms

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.

Topics: Adult; Aged; Bacterial Infections; Bacteroides; Candidiasis; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Enterobacteriaceae; Feces; Female; Humans; Male; Middle Aged; Neoplasms; Pharynx; Staphylococcus; Streptococcus