rifampin and Neutropenia

We have reported a case of isolated bacteremia due to Rhodococcus equi in an immunocompromised, non-HIV-infected patient with acute leukemia. This patient's illness demonstrates a rare presentation of an emerging opportunistic pathogen that may be potentially acquired via exposure to domestic horses or their habitat during periods of aggressive chemotherapeutic administration. The infection was successfully eradicated by treatment with erythromycin and rifampin. Counseling immunocompromised patients inclined to participate in recreational activities involving potential risks of exposure to this pathogen would seem to be a reasonable, but unproven, preventive intervention.

Topics: Actinomycetales Infections; Adult; Animals; Antineoplastic Agents; Bacteremia; Erythromycin; Horses; Humans; Karyotyping; Leukemia, Promyelocytic, Acute; Leukocyte Count; Male; Neutropenia; Remission Induction; Rhodococcus equi; Rifampin

We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host.

Topics: Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Bone Marrow Transplantation; Child, Preschool; Combined Modality Therapy; Female; Fusarium; Humans; Mycoses; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin; Skin; Spider Bites; Staphylococcal Infections

To determine whether the addition of rifampin to a quinolone-based antibacterial prophylactic regimen in patients undergoing high-dose chemotherapy (HDC) with peripheral-blood stem-cell transplantation (PBSCT) decreases the incidence of neutropenia and fever, Gram-positive bacteremia, and infection-related morbidity.. Patients with solid tumors undergoing HDC with PBSCT were randomized to receive prophylactic antibiotics with either ciprofloxacin 500 mg orally every 8 hours or the same ciprofloxacin regimen with rifampin 300 mg orally every 12 hours. Prophylaxis was started 48 hours before stem-cell reinfusion. Patients were monitored to document the occurrence of neutropenia and fever, incidence and cause of bacterial infection, time to onset and duration of fever, requirement for intravenous antimicrobials, and length of hospital admission.. Sixty-five patients were randomized to receive ciprofloxacin and 65 to receive ciprofloxacin plus rifampin, and from these groups, 62 and 61 were assessable, respectively. The proportion of patients who developed neutropenia and fever was 87% in the group treated with ciprofloxacin and 78% in the group treated with ciprofloxacin and rifampin (P =.25). Although there was a trend toward a reduction in the overall incidence of bacteremia (12 v 4 patients), and Gram-positive bacteremia (8 v 2 patients) with the addition of rifampin, none of these comparisons was statistically significant (P =.05 and P =.09, respectively).. The results of this study, which demonstrate that rifampin does not improve ciprofloxacin antibacterial prophylaxis in cancer patients undergoing HDC with PBSCT support but that it does increase the occurrence of undesirable side effects, do not support the routine use of rifampin in this setting.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antineoplastic Agents; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Neoplasms; Neutropenia; Prospective Studies; Rifampin; Statistics, Nonparametric; Treatment Outcome

This open-label, randomized, three-way crossover study of 28 healthy premenopausal women was conducted to compare the impact of concomitant rifabutin and rifampicin on the safety, pharmacokinetics, and pharmacodynamics of the oral contraceptives ethinylestradiol and norethindrone (Ortho-Novum 1/35; Ortho Pharmaceutical, Raritan, NJ). Each participant received oral contraceptives daily for 21 days for the first control cycle, then was randomized to one of two sequences to receive oral contraceptives with concomitant rifampicin and rifabutin at equal doses of 300 mg/day for 10 days. Ethinylestradiol, norethindrone, follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, rifampicin, and rifabutin (and metabolite) were measured in plasma over the same time frames in all three cycles. Safety was assessed from before the beginning to the end of each cycle. Twenty-two subjects completed all three cycles. Compared with the control cycle, rifabutin and rifampicin significantly altered the disposition of the oral contraceptive. Area under the concentration-time curve from 0 to 24 hours (AUC0-24) and maximum plasma concentration (Cmax) of ethinylestradiol decreased by 64% and 42%, respectively, after coadministration with rifampicin and by 35% and 20%, respectively, after coadministration with rifabutin. The AUC0-24 of norethindrone decreased by 60% and 20% after coadministration with rifampicin and rifabutin, respectively. Unlike progesterone levels, FSH and LH levels increased during coadministration with rifampicin and rifabutin. The incidence of spotting was significantly higher after coadministration with rifampicin (36.4%) and rifabutin (21.7%) than during the control cycle (3.7%). Although both rifampicin and rifabutin affected the pharmacokinetics of ethinylestradiol and norethindrone, the magnitude of this effect was more pronounced with rifampicin. Likewise, the fact that the highest incidence of spotting occurred with rifampicin was consistent with higher metabolic induction by rifampicin. Despite the fact that there was no change in progesterone levels, it is recommended that patients be advised to use additional contraceptive methods while receiving rifabutin or rifampicin with oral contraceptives to prevent inadvertent pregnancy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Area Under Curve; Contraceptives, Oral, Synthetic; Cross-Over Studies; Ethinyl Estradiol; Female; Fever; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Middle Aged; Neutropenia; Norethindrone; Rifabutin; Rifampin

We compared ciprofloxacin alone with ciprofloxacin plus rifampin (C + R) as a prophylactic antibacterial regimen for 40 patients with solid tumors treated with high-dose chemotherapy and autologous stem cell transplantation support. No differences were found between groups in the time elapsed to the onset of fever, incidence of febrile episodes, amphotericin B use, and length of hospital stay. However, C + R combination prophylaxis significantly reduced the incidence of gram-positive bacteremia (five versus zero episodes) but was associated with a higher incidence of drug-related side effects.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antineoplastic Combined Chemotherapy Protocols; Ciprofloxacin; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Rifampin

To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram-positive cocci and preserves the protective effect against aerobic gram-negative bacilli.. Open, randomized, controlled, multicenter clinical trial.. Centers participating in the National Cancer Institute of Canada Clinical Trials Group.. 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 10(9)/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting.. One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy.. Incidence and cause of suspected or proven infection.. Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P = 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P < 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norfloxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the ofloxacin plus rifampin group).. Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.

Topics: Adult; Aged; Anti-Infective Agents; Antineoplastic Agents; Bacteremia; Colony Count, Microbial; Female; Humans; Male; Middle Aged; Neutropenia; Norfloxacin; Ofloxacin; Rifampin; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome

We studied the effectiveness of prophylactic oral ciprofloxacin and rifampin on fever prevention in patients undergoing autologous bone marrow transplantation (ABMT) for breast cancer. Furthermore, we evaluated the toxicity and efficacy of empiric once-daily vancomycin and tobramycin for febrile neutropenia.. Ninety-nine assessable women received prophylactic ciprofloxacin and rifampin after high-dose chemotherapy (HDC) for advanced or high-risk primary breast cancer supported with either bone marrow and peripheral-blood progenitor cells (PBPCs) or bone marrow purged with chemotherapy and monoclonal antibodies. Neutropenic fever was treated with empiric once-daily vancomycin and tobramycin. Patients were compared with historic controls treated with the identical HDC and bone marrow support regimen.. In patients treated with bone marrow and PBPCs, the incidence of fever during neutropenia was reduced by ciprofloxacin and rifampin from 98% to 57%. Documented infections were reduced from 42% to 13% (P < .01) and bacteremia from 18% to 0% (P < .001). In purged bone marrow recipients, the overall infection rate decreased from 74% to 17% (P < .001), and bacteremia from 29% to 7%. (P = .02). No patient developed breakthrough bacteremia or sepsis syndrome while on study. Serum creatinine level greater than 1.8 g/dL was noted in 7% of controls and 10% of study patients. Increased ototoxicity was not encountered with the higher peak concentrations of vancomycin and tobramycin.. The therapeutic strategy of ciprofloxacin and rifampin followed by once-daily vancomycin and tobramycin markedly reduced the incidence of infection and virtually eliminated bacteremia in both purged and nonpurged bone marrow recipients. Once-daily vancomycin and tobramycin was safe and effective and, because of the ease of use, facilitates outpatient management of ABMT patients.

Topics: Administration, Oral; Adult; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Bone Marrow Purging; Bone Marrow Transplantation; Breast Neoplasms; Ciprofloxacin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Injections, Intravenous; Middle Aged; Neutropenia; Rifampin; Stem Cell Transplantation; Tobramycin; Vancomycin

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P = .2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

Topics: Administration, Oral; Blood Sedimentation; Chronic Disease; Clinical Trials as Topic; Combined Modality Therapy; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nafcillin; Neutropenia; Osteomyelitis; Random Allocation; Rifampin; Staphylococcal Infections; Time Factors

Coagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices.. A 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient's symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72.. To the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.

Topics: Adolescent; Anti-Bacterial Agents; Child; Coagulase; Cross Infection; Hospitals; Humans; Linezolid; Male; Meningitis, Bacterial; Neutropenia; Rifampin; Staphylococcal Infections; Staphylococcus; Staphylococcus haemolyticus; Vancomycin

We investigated adverse events in patients with prosthetic joint infections receiving combination therapy with linezolid, rifampicin, and clindamycin for ≥ 7 days. Twenty-two patients were evaluated. The combination therapy was administered for 15.5 (7-29) days at dosages of 1200, 450, and 450-1200 mg/day for linezolid, rifampicin, and clindamycin, respectively. Adverse events (gastrointestinal, eye, and skin disorders; liver damage; myelosuppression; hyponatremia, and others) were recorded. The incidence rates of leukopenia, neutropenia, anemia, thrombocytopenia, and hyponatremia were 36.4%, 31.8%, 40.9%, 18.2%, and 18.2%, respectively. Common Terminology Criteria for Adverse Events version 5.0 Grade 3 neutropenia, anemia, and hyponatremia were observed. The incidence rate of myelosuppression was higher following combination therapy compared with that previously reported following single-drug administration. All patients were discharged after the infection was under control. It is important to monitor these adverse events during combination therapy with the aforementioned agents; these conditions may be relieved by discontinuing linezolid.

Topics: Anemia; Anti-Bacterial Agents; Arthritis, Infectious; Clindamycin; Humans; Hyponatremia; Linezolid; Neutropenia; Rifampin

The purpose of this study was to examine the pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection model.. Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA [Mu50]) with rifampicin MIC 0.06 to >256 μg/mL were tested. The efficacy was calculated as the change in bacterial density. A maximum effect model was used to determine the PK/PD index that best described the dose-response data.. The area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax/MIC) were the best correlated with in vivo efficacy (AUC/MIC, R(2) = 0.96; Cmax/MIC, R(2) = 0.97) for S. aureus ATCC 25923 strain, and the dose fractionation-response study did not show significantly different antimicrobial activity (p = 0.10). The AUC/MIC values associated with stasis and 1-log kill for the S. aureus ATCC 25923 strain were 386 and 952, respectively. On the other hand, no antimicrobial efficacy was observed against two strains (MRSA and VISA) with MIC of 128 μg/mL or more.. Rifampicin demonstrated concentration-dependent killing. The AUC/MIC was a predictive PK/PD index.

Topics: Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred ICR; Neutropenia; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Thigh

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin+rifampicin and imipenem+rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem+rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem+rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Immunosuppression Therapy; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Neutropenia; Pneumonia, Bacterial; Rifampin; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Cellulitis; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neutropenia; Phlebitis; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Treatment Outcome

Neutropenia is a rare complication of anti-tuberculous therapy and is usually due to a single agent, most frequently isoniazid. The current case describes a previously healthy immunocompetent patient with tuberculosis of the lymph nodes who developed neutropenia due to a number of first line antibiotics (rifampicin, isoniazid and ethambutol) and streptomycin when introduced in combination and individually thus resulting in repeated treatment disruption. The introduction of twice-weekly subcutaneous granulocyte-colony stimulating factor to correct iatrogenic neutropenia facilitated the continuation and eventual completion of therapy without adverse effect. This is the first description of the use of granulocyte-colony stimulating factor to correct iatrogenic neutropenia due to anti-tuberculous antibiotics and the second description of the occurrence of iatrogenic neutropenia to more than anti-tuberculous antibiotic in an individual.

Topics: Adult; Antibiotics, Antitubercular; Antitubercular Agents; Ethambutol; Granulocyte Colony-Stimulating Factor; Humans; Iatrogenic Disease; Isoniazid; Male; Neutropenia; Rifampin; Streptomycin; Tuberculosis, Lymph Node

Activity of rifampin against 129 Streptococcus mitis isolates obtained from patients with hematologic cancer was investigated. One hundred twenty-five strains were susceptible to rifampin, and 4 were resistant (MIC = 32 to 64 microg/ml). Resistance to rifampin was related to mutations in the rpoB gene: His(526)Asn in three strains and His(526)Asp in one strain.

Topics: Antibiotics, Antitubercular; DNA Primers; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Mutation; Neutropenia; Rifampin; Sequence Analysis, Protein; Streptococcal Infections; Streptococcus mitis

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bone Marrow Transplantation; Catheterization, Central Venous; Catheters, Indwelling; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance; Female; Humans; Infection Control; Leukemia; Male; Middle Aged; Minocycline; Neutropenia; Rifampin; Staphylococcal Infections; Texas

A 10-year-old girl with chronic myelogenous leukemia began receiving cyclosporine the day before bone marrow transplant surgery Three days after the transplant, she developed fever and neutropenia due to a Staphylococcus aureus bacteremia. Despite treatment with various antibiotics, the patient's fever persisted over the next 4 days. Intravenous rifampin was added to her antibiotic regimen of piperacillin, tobramycin, cloxacillin, and amphotericin. On day 12, the patient's blood cultures were negative and her fever had resolved; rifampin was discontinued. On day 16, the patient engrafted; she subsequently developed a grade II graft-versus-host disease of the skin and gastrointestinal tract, which responded to methylprednisolone. Her cyclosporine blood levels, which had been subtherapeutic since day 5 despite increasing intravenous dosages, were within the therapeutic range on day 21, and she was discharged 12 days later. To our knowledge, this is the first documented case of an intravenous cyclosporine-rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a child receiving a bone marrow transplant who subsequently developed acute graft-versus-host disease.

Topics: Antibiotics, Antitubercular; Bacteremia; Bone Marrow Transplantation; Child; Cyclosporine; Drug Interactions; Female; Fever; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infusions, Intravenous; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neutropenia; Rifampin; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Cefotaxime; Child, Preschool; Gram-Positive Bacterial Infections; Humans; Male; Meningitis, Bacterial; Micrococcaceae; Neutropenia; Rifampin; Vancomycin

Topics: Adult; Anti-Bacterial Agents; Appendicitis; Drug Therapy, Combination; Enterocolitis; Humans; Male; Nafcillin; Neutropenia; Osteomyelitis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Tibial Fractures

To analyse the impact of intensified prophylaxis with ofloxacin plus rifampin (O+R) in neutropenic patients we used this combination in 40 consecutive cycles of ifosfamide, cytarabine, prednisolone and etoposide (IAPVP-16). This salvage chemotherapy regimen for lymphoma usually produces four to six days of severe neutropenia without significant extrahematologic toxicities. We compared the infectious morbidity during neutropenia under O+R with 58 consecutives cycles using either norfloxacin or no prophylaxis (control group). Fifty-three percent of control group patients and 20% of the O+R group developed febrile neutropenia that required hospital admission (p<0.001, 95% CI for the difference between both proportions of 16% to 51%). Bacteremia was documented in two patients in the O+R group and six in the control group (p=0.08). Gram-positive cocci (GPC) accounted for all six bacteremias in the control group, while both cases in O+R group were due to a quinolone-resistant gram-negative bacteria (GNB) (p<0.01 for GPC). Five patients (13%) who received O+R and 23 (40%) in control group developed fever of unknown origin, p<0.001, while the total duration of hospitalization due to febril neutropenia was 42 days and 158 days, respectively (p<0.001). In conclusion, intensified prophylaxis with O+R appears to reduce the rate of febrile neutropenia and GPC bacteremia in patients with short and severe neutropenia, which translates into a reduction in the need for hospitalization.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Carmustine; Cyclophosphamide; Etoposide; Female; Fever; Hodgkin Disease; Humans; Length of Stay; Lymphoma; Male; Middle Aged; Neutropenia; Ofloxacin; Opportunistic Infections; Rifampin; Salvage Therapy

We developed an experimental model of candidiasis in rabbits with prolonged neutropenia. Rabbits were made neutropenic with cytosine arabinoside (Ara-C) administered through an indwelling silastic catheter that had been surgically implanted in the external jugular vein. Neutropenia was sustained with intravenous Ara-C, and bacterial complications were prevented with parenteral ceftazidime plus ampicillin. Candidiasis was established by intravenously administering Candida albicans or Candida tropicalis (1-2 x 10(5) colony-forming units) and resulted in hepatic and splenic lesions that mimicked those associated with hepatosplenic candidiasis in humans. The kidney proved to be the site most refractory to eradication of Candida spp. and offered a target organ for assessing antifungal therapy. We evaluated amphotericin B, 5-flucytosine, ketoconazole, and rifampin, alone and in combination. Although each agent reduced the colony counts of Candida in the liver, spleen, and lung, the combination of amphotericin B and 5-flucytosine was the only regimen effective in eradicating renal candidiasis.

Topics: Agranulocytosis; Amphotericin B; Animals; Antifungal Agents; Candidiasis; Cytarabine; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Flucytosine; Ketoconazole; Neutropenia; Rabbits; Rifampin

The efficacy of ticarcillin (100 mg/kg), tobramycin (1 mg/kg), and rifampin (43 and 7.2 mg/kg) individually and in combination was assessed in neutropenic mice infected with an LD90 of one of four Pseudomonas aeruginosa isolates. The study end point was survival at 120 hours after infection. Treatment with the triple combination, ticarcillin plus tobramycin plus rifampin (43 mg/kg), was significantly superior to the double combination of ticarcillin plus tobramycin (p less than 0.01). Although treatment with rifampin (43 mg/kg) alone yielded results similar to treatment with the triple combination in mice infected with three of the four isolates, rifampin-resistant mutants (minimal inhibitory concentration greater than 1000 micrograms/ml) of P. aeruginosa were frequently isolated from surviving mice (26% of mice sampled). In contrast, in mice treated with the triple combination, rarely were rifampin-resistant mutants isolated (3% of mice sampled). Rifampin alone was active against P. aeruginosa isolates only when peak serum concentrations of rifampin exceeded the rifampin minimal bactericidal concentration of the infecting isolate. The addition of rifampin to a "standard" therapy of antipseudomonal penicillin plus aminoglycoside may be useful in the treatment of serious P. aeruginosa infection.

Topics: Animals; Cyclophosphamide; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endotoxins; Exotoxins; Female; Mice; Microbial Sensitivity Tests; Neutropenia; Penicillin Resistance; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Ticarcillin; Tobramycin

Topics: Aged; Agranulocytosis; Antibiotics, Antitubercular; Ethambutol; Humans; Isoniazid; Leukocyte Count; Male; Neutropenia; Neutrophils; Rifampin; Tuberculosis, Pulmonary

Topics: Anemia; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Aspirin; Bone Marrow Diseases; Hematologic Diseases; Humans; Leukemia, Myeloid, Acute; Neutropenia; Rifampin; Thrombocytopenia

Topics: Agranulocytosis; Blood Bactericidal Activity; Candida; Chediak-Higashi Syndrome; Chromosome Aberrations; Chromosome Disorders; Female; Glucosephosphate Dehydrogenase Deficiency; Glutathione Peroxidase; Granulomatous Disease, Chronic; Heterozygote; Humans; Infant, Newborn; Leukocytes; Lupus Erythematosus, Discoid; Male; Neoplasms; Neutropenia; Neutrophils; Peroxidases; Phagocytosis; Pregnancy; Rifampin; Sulfonamides; Vitamin B 6 Deficiency

Topics: Bone Marrow; Bone Marrow Examination; Cholestasis; Erythema; Ethambutol; Humans; Isoniazid; Leukopenia; Male; Middle Aged; Neutropenia; Peritonitis, Tuberculous; Rifampin; Streptomycin; Thrombocytopenia; Tuberculosis; Tuberculosis, Hepatic; Tuberculosis, Osteoarticular; Tuberculosis, Splenic; Vitamin B Complex