Oral trimethoprim/sulfamethoxazole in attempt to prevent infection after induction chemotherapy for acute leukemia

The efficacy of orally administered trimethoprim/sulfamethoxazole for infection prevention following induction chemotherapy was evaluated in 43 patients with acute leukemia. Twenty patients were randomly assigned to treatment with trimethoprim/sulfamethoxazole during 20 episodes of profound granulocytopenia; 23 patients in the control group were followed through 25 granulocytopenic episodes. The incidences of superficial skin and overall infections were significantly lower in those patients with multiple relapses who received trimethoprim/sulfamethoxazole (p = 0.008); however, there was no difference between the groups in regard to days of fever, days of antibiotic administration, days of hospitalization, or gram-negative rod bacteremia. As a result of this study, this regimen cannot be unequivocally recommended for infection prevention in neutropenic patients with acute leukemia undergoing induction or reinduction chemotherapy.     

Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia

Since early diagnosis of even a disseminated fungal infection is difficult and treatment often ineffective in a patient with persistent granulocytopenia, we have prospectively evaluated continued antibiotic therapy and early empiric antifungal therapy in patients with prolonged fever and granulocytopenia. Between November 1975 and December 1979, all patients with fever (oral temperature >38 °C three times per 24 hours or >38.5 °C once) plus granulocytopenia (polymorphonuclear leukocytes < 500/mm³), were evaluated and began an empiric antibiotic regimen consisting of Keflin^®, gentamicin and carbenicillin (KGC). Of the 652 episodes of fever and granulocytopenia (in 271 patients), initial evaluation failed to define an infectious etiology in 323 (49.5 percent). In 50 of the patients in whom initial evaluation did not demonstrate an infectious etiology, fever and granulocytopenia continued after seven days of therapy with KGC, without evidence for the etiology of their persistent fever. These patients were randomized to either discontinue receiving KGC (Group 1); continue receiving KGC (Group 2); continue receiving KGC with the addition of empiric amphotericin B (Group 3). The duration of granulocytopenia was comparable in the three groups (median 24 days, range 8 to 51 days). Clinically or microbiologically demonstrable infections occurred in nine of 16 patients who discontinued the KGC regimen (Group 1) (six also experienced shock, p < 0.01) compared with six of 16 patients who continued the KGC regimen (Group 2) (five in whom fungal infection developed), and in two of 18 patients who continued the KGC regimen plus amphotericin B (Group 3). The incidence of infections was less for patients receiving KGC plus amphotericin B than for patients who discontinued the KGC regimen (p = 0.013).Empiric amphotericin B therapy was also evaluated for its effectiveness in patients whose initial evaluation revealed an infectious etiology with fungal colonization throughout their alimentary tract but in whom fever and granulocytopenia remained despite at least seven days of therapy with appropriate antibiotics. In addition, the postmortem records of all patients dying between 1970 and 1979 were reviewed to ascertain the cause of death and the type of antimicrobial therapy received prior to death. Only one death due to fungal invasion occurred, when therapy with amphotericin B was instituted after one week of broad-spectrum antibiotic therapy.Collectively, these data suggest that continuing antibiotic therapy reduces early bacterial infections in patients with persistent fever and granulocytopenia and that empiric antifungal therapy also appears necessary to prevent fungal superinfections and to control clinically undetected fungal invasion.     

Ceftazidime with or without amikacin for the empiric treatment of localized infections in febrile,granulocytopenic patients

Summary In a prospective randomized study, 90 granulocytopenic febrile patients presenting with a localized infection were treated empirically with ceftazidime alone or in combination with amikacin (1.5 g/day). Two thirds had received selective oral antimicrobial prophylaxis before therapy. The treatment groups were comparable in terms of the depth and duration of granulocytopenia as well the distribution of the infection categories and rate of bacteremia. There was no difference with respect to the final response: 53% for the monotherapy group versus 48% for the combination group, and both regimens appeared to be equally safe. The duration of fever, clinical symptoms, antibiotic therapy, and granulocytopenia were comparable for both treatment groups, and approximately 90% of patients survived the infection. Only one patient given monotherapy required amikacin. It is concluded that aminoglycosides are not necessary for the empiric treatment of infectious complications in granulocytopenic patients if antibacterial prophylaxis has been given before-hand.J. P. Donnelly is supported by Glaxo Group Research, London, United Kingdom     

Lessons learned from surveillance cultures in patients with acute nonlymphocytic leukemia. Usefulness for epidemiologic, preventive and therapeutic research

In 135 consecutive patients with acute nonlymphocytic leukemia (ANLL), who were admitted to the Baltimore Cancer Research Program (BCRP) for their first induction chemotherapy shortly after initial diagnosis and who had received no recent antibiotic therapy, surveillance cultures were obtained of specimens from the nose, gingiva, axillas and rectum twice during the first week of hospitalization and then twice weekly thereafter. All organisms which were morphologically distinct on routine culture media were fully identified, and Pseudomonas aeruginosa was serotyped. Baseline surveillance cultures indicated that there was a higher than expected incidence of colonization with gram-negative bacilli in the nose, gingiva and axillas along with the expected colonization by gram-negative bacilli in the rectum. Among these colonizing gram-negative bacilli, Ps. aeruginosa and, to a lesser extent, Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis were most likely to be associated with a subsequent bacteremia during periods of mucosal damage and granulocytopenia. Follow-up surveillance cultures indicated that new organisms were acquired at a rate of 0.5 organism per patient per week with many of these acquired organisms being gram-negative bacilli of the type likely to cause infection in these patients. Compared to similar surveillance cultures obtained in a previous group of patients not subjected to vigorous infection prevention techniques, the rate of new organism acquisition was less and the development of infection subsequent to colonization was reduced. Surveillance cultures also indicated those patients at highest risk of having yeast infections such as those caused by Torulopsis glabrata or Candida species. Results of nasal surveillance cultures detected a subpopulation of patients at greatest risk for colonization and subsequent infection with Aspergillus flavus. Surveillance cultures have been utilized for the design of systemic therapeutic antibiotic protocols and for the monitoring of oral nonabsorbable antimicrobial regimens for alimentary canal microbial suppression. Despite the usefulness of surveillance cultures for research in the epidemiology, prevention and treatment of infection in patients with acute leukemia, their routine use in a nonresearch setting would not be advised.     

Teicoplanin compared to flucloxacillin for antibiotic treatment of neutropenic patients

S ummary Ninety-eight neutropenic patients were randomized to receive piperacillin and gentamicin in combination with either teicoplanin or flucloxacillin. Sixty-scven of these patients, most of whom had myeloma. were given this combination as prophylaxis 5 d after high dose chemotherapy. 3 5 receiving flucloxacillin and 32 receiving teicoplanin. Of 31 patients with leukaemia who were febrile and neutropenic following induction chemotherapy or bone marrow transplantation. 18 received flucloxacillin and 13 received teicoplanin. For those given flucloxacillin. the mean number of days to change of antibiotics was 7.8 in the prophylaxis group and 5.1 in the treatment group. In the teicoplanin arm, the mean number of days to change antibiotics was 6.8 in the prophylaxis group and 6.1 in the treatment group. Two patients in the flucloxacillin arm developed drug rashes. Four patients developed rigors after teicoplanin administration and one asthmatic became wheezy. One patient had a progressive rise in creatinine, but overall the patients having teicoplanin did not have any appreciable increase of renal toxicity compared to the flucloxacillin arm. Blood cultures were positive prior to commencement in the treatment group in nine patients, and during treatment in six patients. Organisms grown were Gram-positive in 14 patients. Teicoplanin appears to be as effective as flucloxacillin when each is used in combination with piperacillin and gentamicin in the treatment of neutropenic patients, with similar rates of toxicity.     

Antibiotic strategy after the empiric phase in patients treated for a hematological malignancy

 Empiric broad-spectrum antibiotic therapy has become a generally accepted strategy in the treatment of febrile neutropenic patients. Particularly in patients with prolonged neutropenia, subsequent adaptation of such a regimen will be the rule rather than exception. Since there are no uniformly accepted guidelines for the modification of antibiotic therapy during the post-empiric phase, we assessed the impact of a set of rules that evolved during the first randomized trials. Evaluation of the clinician's compliance with these rules in 1951 febrile neutropenic episodes was the subject of the present analysis. Treatment was modified in 761 (39%) cases, and these changes were made according to the rules in 76%. For 75% of the alterations in treatment during the evening and night shifts, no reasonable explanation was established, while 93% of the modifications during the normal working hours were made for objective reasons. The empiric regimen was more frequently changed in patients with a clinical focus of infection at the onset of fever than in patients who showed fever as the only symptom of a possible infection. The perceived need for modification amounted to 69% in pulmonary infections, to 51% in skin and soft-tissue infections, to 44% in patients with abdominal complaints, and to 37% in upper respiratory tract infections. Glycopeptides constituted 22% of modifications, particularly in patients with a central venous catheter, and systemically active antifungals were administered in 16% of cases. Especially inexperienced clinicians tend to adjust antibiotic therapy, in spite of the fact that persistence of fever alone seldom reflects inadequate treatment when the clinical condition of the patient is stable or improving. On the other hand, the development of subsequent infectious events emphasizes that a genuine need for modification does frequently exist. Received: 4 December 1995 / Accepted: 7 December 1995     

Usefulness of G-CSF in pediatric high risk cancer patients with fever and neutropenia

Chemotherapy associated febrile neutropenia is an important cause of morbidity and mortality in pediatric patients with cancer. The use of granulocyte-colony stimulating factor (G-CSF) post chemotherapy decreases the risk of infectious complications but its efficacy during the febrile neutropenic episode remains controversial. Thirty five episodes of high-risk febrile neutropenia were randomized into two treatment arms, 18 received antibiotics and G-CSF (group A) and 17 received antibiotics only upon admission (group B). Both groups were comparable in terms of demographic and clinical characteristics. No significant differences between groups were found in duration of hospitalization (mean group A 7 vs group B 8 days), antibiotic treatment (mean 7 vs 8 days), fever (3 vs 2 days), nor of neutropenia (4 vs 3 days). One patient in group A died after RSV infection. Considering these results and a literature review, we propose that G-CSF should not be recommended in children during the course of their febrile neutropenic episode.     

伊曲康唑预防血液肿瘤患者粒细胞减少期并发真菌感染的疗效观察

目的:探究应用伊曲康唑口服液预防血液肿瘤患者化疗后粒细胞减少期并发真菌感染的效果.方法:将62例化疗后中性粒细胞减少的血液肿瘤患者随机分为真菌感染预防用药组和对照组,其中预防用药组患者预防性地服用伊曲康唑口服液,而对照组患者未接受任何预防性抗真菌药物治疗.观察并比较2组患者真菌感染的发生率和严重程度.结果:31例服用伊曲康唑口服液患者中,仅2例发生真菌感染,真菌感染率仅为6.5%,而对照组31例中,8例并发真菌感染,包括3例深部真菌感染,真菌感染率为25.8%,明显高于预防用药组(P<0.01),而且2组患者并发真菌感染的病原菌存在明显差异.结论:预防性应用伊曲康唑口服液能有效降低血液肿瘤患者化疗后粒细胞减少期真菌感染的概率.     

Lethal pulmonary hemorrhage caused by Stenotrophomonas maltophilia pneumonia in a patient with acute myeloid leukemia

A 63-year-old man had been treated with intensive chemotherapy for acute myeloid leukemia. On the 49th hospital day, he had febrile neutropenia after the second course of induction chemotherapy. On the 53 rd hospital day, he presented with hemoptysis and developed acute respiratory failure requiring ventilator support within several hours. On the 54th hospital day, the patient died with hemorrhagic respiratory infection. Stenotrophomonas maltophilia was detected in bacterial cultures of his blood, bronchoalveolar lavage, and sputum. To our knowledge, nine cases of fatal hemorrhagic pneumonia caused by S. maltophilia have been reported in the literature. All the patients had hematological neoplasms and were severely neutropenic after one or two intensive chemotherapy regimens. They died shortly (within 3 days) after the onset of the hemorrhagic pneumonia. Management of the infection caused by S. maltophilia is hampered by high-level intrinsic resistance to multiple antibiotics and the increasing occurrence of acquired resistance to co-trimoxazole and fluoroquinolones. It would be important to keep in mind that hemorrhagic respiratory infection caused by S. maltophilia may lead to a fulminant and lethal course in severely neutropenic patients with hematological neoplasms and to recognize which antibiotic agents are more sensitive to S. maltophilia in each institution.     

Stopping antibiotic therapy in neutropenic patients

Infection is the major cause of death in neutropenic patients. Because of the lack of acute inflammatory cells, the usual signs of infection are often absent in these patients. Therefore, unexplained fever in a neutropenic patient requires prompt initiation of antibiotic therapy. Many physicians advocate continuing antibiotic therapy until neutropenia resolves. However, prolonged treatment with broad-spectrum antibiotics increases the risks of drug toxicity and superinfection with resistant bacteria and fungi. Based on a critical review of the literature and a large personal clinical experience, I offer tentative guidelines for withdrawing antibiotic therapy in persistently neutropenic patients. When antibiotic therapy is discontinued, frequent and careful monitoring of these patients and a low threshold for reinstituting antibiotic therapy are essential.     

Therapeutic role of granulocyte transfusions

Granulocyte transfusions are used as adjuvant therapy for infection in neutropenic patients with underlying neoplastic disease, neutropenic infants, and patients with qualitative white blood cell disorders. In addition, prophylactic leukocyte transfusions have been administered to patients during remission induction for acute leukemia or after bone marrow transplantation. The role of granulocyte therapy will need constant reassessment as new antibiotics and other forms of treatment are developed. At present, granulocyte transfusions are indicated in the treatment of severely neutropenic patients with documented bacterial infection who are unlikely to recover hematopoietic function over the next week and are deteriorating despite 48-72 hr of optimal antibiotic therapy. Under these conditions, they improve the rate of survival from the infectious episode without clearly affecting the longer-term survival of the patient. Only a small minority of neutropenic patients will require granulocyte transfusions.     

Duration of empiric antibiotic therapy in granulocytopenic patients with cancer.

Early initiation of empiric antibiotic therapy in febrile cancer patients has become established practice, but the appropriate duration of antibiotic therapy when no infectious source can be identified is unknown. The complications of broad-spectrum antibiotics argue for brief treatment, but the risk of an inadequately treated infection in the granulocytopenic patient favors longer therapy. We prospectively studied 306 episodes of fever and granulocytopenia in 143 patients with leukemia or solid tumor (age one to 33 years) with respect to the duration of empiric antibiotic treatment. Eligible patients (fever > 38 °C three times/24 hours or > 38.5 °C once, plus polymorphonuclear leukocytes < 500/mm³) had an extensive diagnostic evaluation, including at least two preantibiotic blood cultures, and therapy was then started with a broad-spectrum antibiotic regimen— Keflin^®, gentamicin and carbenicillin (KGC). Initial evaluation failed to identify an infectious etiology for the fever in 142 of 306 (46 per cent) episodes. Fifty-six of 142 (39 per cent) of these fevers of unknown origin were associated with persistent granulocytopenia for more than seven days; in 33 of these, defervescence occurred while the patients received KGC. After seven days of empiric KGC therapy, the 33 patients with fevers of unknown origin who had become afebrile with empiric antibiotics but whose polymorphonuclear leukocytes remained less than 500/mm³ were randomized to either continue or discontinue ($\text{d}\text{c}$) to receive KGC. The patients who continued to receive KGC until their polymorphonuclear leukocytes were more than 500/mm³ had no infectious sequelae. However, in seven of 17 (41 per cent) of the patients randomized to $\text{d}\text{c}$ KGC infectious sequelae developed (p = 0.007) within a median of two days of discontinuing KGC (two with fever which again responded to KGC therapy, and five with a documented infection [two ultimately fatal]). In none of the patients did a resistant microbial flora or superinfection develop. These data suggest that the patient with a fever of unknown origin who becomes afebrile during empiric antibiotic therapy may profit from continued therapy while granulocytopenia persists.     

Empirical antibiotic therapy in febrile neutropenic patients with acute leukemia

One hundred and ninety-five episodes of fever during the neutropenic phase of chemotherapy in 49 patients with acute leukemia from 1984 to 1987 were analyzed with the following results: 1) Febrile episodes occurred in 80 percent of the neutropenic (less than 500/microliters) phase lasting more than 7 days after chemotherapy. 2) Febrile episodes consisted of 44 (22%) of established septicemia and 111 (57%) of suspected septicemia. 3) The pathogens causing septicemia were 8 GPC, 38 GNB (22 Pseudomonas species) and 6 fungi. Fungemia was confirmed on an average of 4.8 days after the onset of fever. The mortality of septic events was 10 out of 17 episodes (59%) when treated with antibiotics alone, while 8 out 27 (30%) with the combination of antibiotics plus antifungal drugs. 4) The mortality of suspected sepsis was only 2 out of 111 episodes. Eighty-three (75%) of these 111 episodes responded to antibiotics alone, while 26 (23%) cases needed antibiotics plus antifungal drugs. Our results suggest that in febrile neutropenic patient empiric broad-spectrum antibiotic therapy should be initiated which is especially effective for Pseudomonas species, but if fever persists despite more than 4 or 5 days of antibiotic therapy, additional antifungal therapy should be considered.     

Safe and feasible outpatient treatment following induction and consolidation chemotherapy for patients with acute leukaemia

Traditionally, patients with acute leukaemia are admitted to hospital during chemotherapy‐induced pancytopenia, although a few recent reports have reported the feasibility and safety of outpatient treatment. We have developed an outpatient treatment programme for patients with acute leukaemia incorporating comprehensive patient education for self‐care management at home during pancytopenia and involvement of patients in care of their tunnelled central venous catheter (CVC). During neutropenia, patients are treated with prophylactic ciprofloxacine, amoxicillin/clavulanic acid and fluconazole. Herein, we report the results of outpatient treatment of 60 patients with acute leukaemia (54 with acute myeloid leukaemia) followed prospectively in the period from March 2004 to 2007. After induction chemotherapy, outpatient treatment was possible after 48 of 73 induction courses, with no readmission in 19 of these (40%). A total of 129 consolidation courses were administered with outpatient treatment following 116 of these, with no readmission in 69 (59%). The median number of days spent at home with neutrophils below 0.5 × 10⁹/L was 8 d per course following induction and 12 d following consolidation chemotherapy. The predominant cause of readmission was neutropenic fever, in most instances of unknown origin. Coagulase‐negative staphylococci and Enterococcus faecium were the most frequently identified bacteria in blood cultures, whereas only four positive blood cultures with multiresistant Escherichia coli were identified in the entire patient cohort, the latter exclusively observed in patients receiving antibiotic prophylaxis. The majority of the patients were able to take care of their CVC including change in dressing and heparin flushing. There were 12 CVC‐related infections. There were no treatment‐related deaths. We conclude that outpatient treatment of patients with acute leukaemia is feasible and safe.     

Oral cefixime is similar to continued intravenous antibiotics in the empirical treatment of febrile neutropenic children with cancer.

Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization, but the safety of this approach has not been adequately studied in children. We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation. Two hundred episodes of febrile neutropenia were studied (156 patients), and 100 episodes were randomized to receive each treatment. Failure to respond to therapy was defined by documented or suspected bacterial infection, recurrent fever, or discontinuation of assigned therapy for any reason before neutropenia resolved. Rates of treatment failure were similar in the oral cefixime group (28%) and in the iv antibiotic group (27%; P=1.0). Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children, a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment.     

Short courses of antibiotics in selected febrile neutropenic patients.

To evaluate their policy of discontinuing broad spectrum antibiotics in patients with negative cultures who become afebrile but remain neutropenic, the authors retrospectively reviewed the charts of all pediatric patients diagnosed with cancer between 1980 and 1986. Two hundred seventy-one children had 385 admissions for infectious complications during the study period. In 39 of those episodes (9%), the patients had negative cultures, became afebrile, and were discharged with absolute neutrophil counts of less than 1000 cells/mm3 (mean 390 cells/mm3). They received relatively short courses of antibiotics with a median duration of 4 days. Only four of these patients became febrile during the followup period and there were no fatalities. Given the benign course of these patients, recommendations for prolonged antibiotic courses should be reconsidered.     

Utility of obtaining blood cultures in febrile neutropenic patients undergoing bone marrow transplantation

Infection remains an important cause of morbidity and mortality after bone marrow or stem cell transplantation. To evaluate the role of obtaining blood cultures for intermittent or persistent fever in neutropenic patients on antibiotic therapy, we performed a retrospective chart review of 196 consecutive patients admitted to the Bone Marrow Transplant Unit at the University of North Carolina Hospitals from 1995 to 1998. From the cohort of 196 patients, 154 patients developed neutropenic fever. The initial blood culture was positive in 16 of 145 patients during the first fever episode giving a prevalence of 11%. From the total of 109 patients that had blood cultures drawn after day 1 of fever, five patients had blood cultures positive for a pathogen, a prevalence of 4.6%. In only one patient, did blood cultures drawn after day 1 identify an organism not present on day 1 (prevalence 0.9%). After reviewing the results in the first 105 patients, we changed our timing of collection of blood cultures. Forty-nine patients were treated in this manner and we found that the mean number of blood cultures decreased from 9.2 to 4.7 per patient without a change in the frequency of infectious complications or length of hospitalization.     

A prospective, randomized study comparing cefepime and imipenem-cilastatin in the empirical treatment of febrile neutropenia in patients treated for haematological malignancies

A prospective, open label, randomized, multicentre study was conducted, comparing the efficacy and safety of cefepime with that of imipenem-cilastatin for the management of febrile neutropenia in patients with haematological malignancies. Furthermore, the safety of early discontinuation of antibiotic therapy in patients with fever of undetermined origin (FUO) was assessed. A total of 180 patients with 207 febrile episodes were randomized at start of fever (105 episodes for cefepime and 102 episodes for imipenem). The 2 groups were comparable in terms of age, gender, underlying malignancy, prior transplantation, and presence of central venous catheters. All patients were neutropenic at inclusion with median absolute neutrophil count (ANC) 0.1 x 10(9)/l(range 0-1 x 10(9)/l), and ANC < or = 0.1 x 10(9)/l in 77% of included patients. The mean duration of neutropenia, with ANC < 0.5 x 10(9)/l was 6.2 d. Febrile episodes were classified as microbiologically documented infection (47%), FUO (43%), or clinically documented infection (10%). At final evaluation 1-2 weeks after completion of antibiotic therapy, monotherapy success rates were 40% and 51% in the cefepime and imipenem-cilastatin groups respectively (p = 0.33). The 4-week overall mortality rate was 5%. Three (2%) of the cefepime treated patients and 4 (3%) of the imipenem-cilastatin treated patients died as a result of infection. Adverse events directly related to antibiotic treatment were uncommon and did not differ between groups. Early discontinuation of antibiotic therapy in 31 patients with FUO 48 h after defervescence was not associated with an increased rate of fever relapse or mortality compared with a subgroup of 29 patients where therapy was continued.     

Quality control in tuberculosis bacteriology. 2. The origin of isolated positive cultures from the sputum of patients in four studies of short course chemotherapy in Africa

During intensive bacteriological follow-up of 2123 patients who had received short course chemotherapy regimens in 4 controlled clinical trials in Africa and had not had a bacteriological relapse, 405 isolated positive cultures were obtained from 37 429 sputum specimens in 3 East African laboratories. These cultures might have arisen as a result of clerical error, of transfer of bacilli from positive to negative specimens in the laboratory or from the lesions of the patients. Clerical error in the labelling of specimens or the recording of results did not seem a frequent cause, since isolated positive cultures contained many fewer colonies than cultures from other positive specimens being processed at the same time. Several of evidence suggested that some isolated positive cultures arose from the lesions of patients: a decrease in their incidence occurred in successive time periods after chemotherapy; the number of isolated positives per patient departed significantly from the Poisson distribution; they were more often drug resistant than other cultures processed at the time; positive cultures were obtained less frequently from known autoclaved specimens inserted among the the study specimens than from the study specimens themselves; no association was found between the incidence of isolated positive and of specimens containing numerous viable M. tuberculosis being processed at the same time. Nevertheless some of these cultures probably arose by transfer in the laboratory, since the rates at which transfer were known to occur differed in the 3 laboratories and corresponded to the rates of obtaining isolated positive cultures.     

Prophylactic use of ofloxacin in granulocytopenic patients with hematological malignancies during post-remission chemotherapy.

The prophylactic efficacy of ofloxacin (OFLX) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospective, randomized, controlled trial. Oral administration of OFLX plus amphotericin-B (AMPH) and polymyxin-B (PL) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone (p less than 0.01), and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia (p less than 0.01). Furthermore, the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen (p less than 0.05). Clinically, the prophylactic efficacy was 92% for the OFLX regimen and 40% for the control regimen (p less than 0.01). These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy. Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy.