acyclovir and Neutropenia

A 55-year old man developed a hemorrhagic pneumonia, likely due to infection with Kytococcus sedentarius during neutropenia following induction chemotherapy for acute myeloid leukemia. Severe mucosal barrier injury and the selective pressure of broad-spectrum antibiotics probably made it possible for this normally harmless commensal to penetrate the gut, spread through the blood stream, and invade the lungs.

Topics: Actinomycetales; Actinomycetales Infections; Acyclovir; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bacterial Translocation; Cefepime; Cephalosporins; Clostridium Infections; Colistin; Cytarabine; Daunorubicin; Drug Therapy, Combination; Etoposide; Fatal Outcome; Hemoptysis; Humans; Hydroxyurea; Immunocompromised Host; Intestinal Mucosa; Leukemia, Myeloid, Acute; Male; Metronidazole; Middle Aged; Neutropenia; Pneumonia, Bacterial; Superinfection; Teicoplanin; Trimethoprim, Sulfamethoxazole Drug Combination

Virus infections account for considerable morbidity in bone marrow transplant (BMT) recipients. In all ages, members of the herpes virus group are the predominant pathogens. Of these, cytomegalovirus is pre-eminent in being the most frequent cause of death due to infection associated with the transplant procedure. Considerable effort is being invested in the development of preventative and therapeutic strategies to control this virus. Other potentially life-threatening virus infections may be acquired on the transplant unit as a result of cross-infection and can be caused by enteroviruses, rotaviruses and adenoviruses. Prevention of these infections is best achieved by implementation of strict infection-control measures.

Topics: Acyclovir; Adult; Bone Marrow Transplantation; Child; Cytomegalovirus Infections; Ganciclovir; Graft vs Host Disease; Herpes Simplex; Humans; Neutropenia; Respiratory Syncytial Viruses; Respiratory Tract Infections; Respirovirus Infections; Tissue Donors; Virus Diseases

The possible mechanisms of neutropenia associated with both human immunodeficiency virus (HIV) infection and drug treatment in adults are examined, and the current and investigational strategies for managing neutropenia are reviewed. Neutropenia associated with HIV arises from diverse mechanisms, including cellular immune dysfunction, direct effects on progenitor cells, humoral immune dysfunction, and vitamin deficiencies. Drug-induced neutropenia may be related to direct cytotoxic effects, immunologic mediators, and the effects of vitamin depletion on the bone marrow. Bone marrow toxicity in patients receiving zidovudine appears to be more frequent in those patients with advanced disease, low CD4 cell counts, a pretreatment anemia, low serum vitamin B12 levels, and low or low normal serum folic acid levels. Patients with AIDS also are at increased risk for adverse events associated with folate antagonists and sulfonamides compared with other patient populations. Lithium therapy has improved neutrophil counts in patients receiving zidovudine; however, the toxicities associated with use of lithium, combined with the lower dosages of zidovudine now recommended, may obviate its use. The use of colony-stimulating factors appears promising for increasing the number and function of circulating neutrophils. Although concomitant use of interferon alfa and zidovudine may result in a strong synergistic anti-HIV effect, dose-limiting neutropenia has been reported in patients receiving the combination. There are currently no controlled data assessing the effectiveness of intravenous immune globulin in the treatment of HIV-related or drug-related neutropenia. In evaluating neutropenia, the clinician must attempt to discern whether the neutropenia is more likely related to disease state(s) or drug therapies. Potential management strategies include modulation of the disease state, discontinuation or dose reduction of the offending agent, or administration of exogenous immune enhancer.

Topics: Acyclovir; HIV Infections; Humans; Neutropenia; Sulfonamides; Zidovudine

It is common practice to administer acyclovir as prophylaxis to patients with hematologic malignancies during neutropenia; however, effective therapy requires frequent dosing, which is difficult in this setting. Valacyclovir has greater oral bioavailability and requires less frequent dosing.. To evaluate the efficacy and safety of valacyclovir compared with acyclovir.. Patients who had been treated with chemotherapy or stem-cell transplantation were randomized to receive acyclovir 400 mg orally 3 times daily (n = 51), valacyclovir 500 mg orally twice daily (n = 48), or valacyclovir 250 mg orally twice daily (n = 52) during neutropenia.. Clinical success, defined as the absence of an active herpes simplex virus (HSV) lesion or asymptomatic viral shedding, was similar between the 3 groups (acyclovir 96%, valacyclovir 500 mg 95%, valacyclovir 250 mg 100%). The overall rates of adverse events were similar in the 3 groups.. Prophylactic treatment with valacyclovir is an effective and safe alternative to acyclovir for the prevention of HSV reactivation in patients with hematologic malignancies.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Agents; Antiviral Agents; Biological Availability; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic Neoplasms; Herpes Simplex; Humans; Male; Middle Aged; Neutropenia; Single-Blind Method; Stem Cell Transplantation; Valacyclovir; Valine

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC)

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Bone Marrow Transplantation; Child; Child, Preschool; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Incidence; Infant; Life Tables; Male; Middle Aged; Minnesota; Neutropenia; Prospective Studies; Survival Analysis; Transplantation, Homologous; Treatment Outcome; Viremia; Virus Latency; Virus Replication

To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem.. Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection.. Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients.. Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.

Topics: Acyclovir; Adolescent; Adult; Aged; Bacterial Infections; Cause of Death; Ceftazidime; Child; Child, Preschool; Female; Fever; Fever of Unknown Origin; Humans; Imipenem; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Vancomycin

Ganciclovir, an acyclic nucleoside with improved activity against cytomegalovirus in vitro, was used to treat 15 marrow transplant patients with symptomatic cytomegalovirus infection of the gastrointestinal tract. Eleven of the 15 had improvement in one or more of their clinical signs or symptoms during treatment. No clinical relapses were observed. Viral excretion from throat, urine and blood stopped at a median of 6 days of treatment, but six patients had recurrence of viral excretion 7-25 days after treatment was stopped. The only toxicity was the development of reversible neutropenia in eight of 15 patients after 10-19 days of treatment. Neutropenia was not related to duration of treatment, plasma drug levels or to the neutrophil count at the beginning of treatment. Although treatment with ganciclovir may be associated with marrow suppression, the serious nature of gastrointestinal infection due to cytomegalovirus in the immunocompromised host, the antiviral effect and the possible clinical improvement observed in vivo, and the lack of other effective treatments justify further controlled studies with this agent in immunocompromised patients with serious cytomegalovirus infection.

Topics: Acyclovir; Antiviral Agents; Bone Marrow Transplantation; Clinical Trials as Topic; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases; Humans; Neutropenia

That acyclovir is effective therapeutically in herpes simplex virus (HSV) and herpes zoster (VZV) infections in immunocompromised patients has been established [13]. This paper reviews our subsequent studies in prophylaxis of herpes group infections in a high risk group of patients suffering from acute leukaemia. In study 1 we randomised HSV seropositive (greater than or equal to 1:8) patients to receive intravenous acyclovir or placebo. In this stratified study bone marrow transplant (BMT) recipients were completely protected from HSV infections by acyclovir compared with a 50% failure rate for those on placebo. There was significant protection also in the non-BMT group [8]. In study 2 oral acyclovir prophylaxis failed to provide complete protection in BMT recipients despite the achievement of apparently adequate blood levels. In study 1 the secretion of EBV in saliva before and during the trial gave inconclusive results. In each of the first two studies one patient on "active" acyclovir developed a cytomegalovirus (CMV) infection. Thus, at the dosage of drug used, prophylaxis of CMV was unsuccessful suggesting that claims of therapeutic efficacy are unlikely to be supported in controlled trials. Study 3 is current and concerns the pharmacokinetics of an acyclovir prodrug (BW 134U) taken by mouth. This drug is near 100% absorbed and achieves approximately twice the level of active acyclovir in vivo, following conversion by adenosine deaminase (ADA), in normal volunteers.

Topics: Acyclovir; Bone Marrow Transplantation; Clinical Trials as Topic; Herpes Simplex; Herpes Zoster; Humans; Immunity; Leukemia; Neutropenia

We explored the adverse drug reaction signals of drug-induced neutropenia (DIN) and drug-induced agranulocytosis (DIA) in hospitalized patients and evaluated the novelty of these correlations.. A two-step method was established to identify the relationship between drugs and DIN or DIA using 5-year electronic medical records (EMRs) obtained from 242 000 patients at Qilu Hospital of Shandong University. First, the drugs suspected to induce DIN or DIA were selected. The associations between suspected drugs and DIN or DIA were evaluated by a retrospective cohort study using unconditional logistic regression analysis and multiple linear regression model.. Twelve suspected drugs (vancomycin, meropenem, voriconazole, acyclovir, ganciclovir, fluconazole, oseltamivir, linezolid, compound borax solution, palonosetron, polyene phosphatidylcholine, and sulfamethoxazole) were associated with DIN, and six suspected drugs (vancomycin, voriconazole, acyclovir, ganciclovir, fluconazole, and oseltamivir) were associated with DIA. The multivariate linear regression model revealed that nine drugs (vancomycin, meropenem, voriconazole, ganciclovir, fluconazole, oseltamivir, compound borax solution, palonosetron, and polyene phosphatidylcholine) and four drugs (vancomycin, voriconazole, ganciclovir, and fluconazole) were found to be associated with DIN and DIA, respectively. While logistic regression analysis revealed that palonosetron and ganciclovir were associated with DIN and DIA, respectively.. Palonosetron and ganciclovir were found to be correlated with drug-induced granulocytopenia. The results of this study provide an early warning of drug safety signals for drug-induced granulocytopenia, facilitating a quick and appropriate response for clinicians.

Topics: Acyclovir; Aged; Agranulocytosis; Electronic Health Records; Ganciclovir; Humans; Meropenem; Neutropenia; Palonosetron; Thrombocytopenia; Vancomycin; Voriconazole

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

Topics: Acute Disease; Acyclovir; Amphotericin B; Antifungal Agents; Appendicitis; Aspergillosis; Aspergillus; Child; Ciprofloxacin; Fluconazole; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Pyrimidines; Voriconazole

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Diagnosis, Differential; Female; Fever; Hepatitis, Viral, Human; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Neutropenia; Recurrence; Risk; Transaminases

The herpesviridae family includes, among others, herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. Herpesviridae viral infections (HVIs) can lead to serious complications in lymphoma patients undergoing chemotherapy. There is no consensus on the dose and duration of antiviral prophylaxis in these patients. We retrospectively analyzed the incidence and risk factors for HVI in lymphoma patients undergoing chemotherapy.. We reviewed the records of 266 patients who were newly diagnosed with lymphoma and received chemotherapy without acyclovir prophylaxis between June 1996 and August 2009.. The cumulative incidence rate of HVI was 20.16% for 5 years from the start of chemotherapy. Independent predictive factors for HVI in lymphoma patients were: female sex [hazard ratio (HR) 2.394; 95% confidence interval (CI): 1.245-4.607; P=0.009], cumulative dose of steroids per body surface area of at least 2500 mg/m(2) (HR 7.717; 95% CI: 3.814-18.703; P<0.001), and history of neutropenic fever (HR 0.297; 95% CI: 0.150-0.588; P<0.001).. Female sex, high dose of steroids per body surface area, and neutropenic fever were risk factors for HVI in patients with lymphoma undergoing chemotherapy without acyclovir prophylaxis.

Topics: Acyclovir; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Female; Fever; Herpesviridae Infections; Humans; Incidence; Lymphoma; Male; Medical Records; Middle Aged; Neutropenia; Odds Ratio; Primary Prevention; Retrospective Studies; Risk Factors; Sex Factors

A previously healthy boy aged 9 years and 11 months was admitted due to herpetic gingivostomatitis with poor intake. He also had fever, neutropenia, and elevated serum aminotransferase level (> 1000 IU/mL). Prolonged prothrombin time, mild gastrointestinal hemorrhage and transient decreased conscious level were noted during hospital days 2 and 3. Intravenous acyclovir therapy commenced on hospital day 2 and his serum aminotransferase level peaked (> 4000 IU/mL) on hospital day 3 and then improved gradually. A throat swab was positive for human herpes simplex virus (HSV)-1, serological test was positive for acute primary HSV-1 infection, and a blood specimen was also strongly positive for HSV-1 by polymerase chain reaction. He received a 14-day course of intravenous acyclovir and recovered uneventfully. Herpetic gingivostomatitis, although mostly benign and self-limited, may be complicated with severe hepatitis, even in immunocompetent hosts.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Child; Fever; Hepatitis; Herpesvirus 1, Human; Humans; Male; Neutropenia; Serologic Tests; Specimen Handling; Stomatitis, Herpetic; Transaminases; Treatment Outcome

Although the standard of care in febrile neutropenic patients includes the initiation of empirical antibacterial and antifungal therapy, many patients do not respond and need further diagnostic work up and treatment. Here, we report on an immunosuppressed neutropenic patient with a prolonged episode of fever unresponsive to empirical antibacterial therapy. Herpes polymerase chain reaction revealed systemic reactivation of herpes simplex virus type 1 (HSV-1) infection and treatment with acyclovir was associated with the prompt resolution of signs and symptoms of infection. Screening for HSV in persistently febrile neutropenic patients may discover HSV reactivation that can be treated successfully by acyclovir administration.

Topics: Acyclovir; Child; Fever; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Neutropenia; Viremia; Virus Activation

Posttransplant leukopenia is frequently observed in renal transplant. Granulocyte colony-stimulating factor controls the production of functional neutrophils and their release into peripheral blood. Granulocyte colony-stimulating factor has been widely and frequently used for many conditions and disorders in the field of hematology and oncology.. We present the cases of valacyclovir-related and valganciclovir-related neutropenia in 2 renal transplant recipients.. Both cases had renal transplants from live donors. The first one was an 18-year-old man. Laboratory investigations revealed his leukocyte count as 1.7 x 10(9)/L. The patient was using mycophenolate mofetil, cyclosporine, and valganciclovir. Mycophenolate mofetil was stopped because he had neutropenia, and later, valganciclovir was also stopped because the neutropenia persisted. Because the neutropenia did not recover after we discontinued valganciclovir, the patient was administered granulocyte colony-stimulating factor. The neutrophil count increased to 2.2 x 10(9)/L (leucocyte count to 6.5 x 10(9)/L) after 24 hours. The second case was a 37-year-old man and was using mycophenolic acid, tacrolimus, and valacyclovir. Laboratory investigations revealed his leukocyte count to be 1.3 x 10(9)/L. Mycophenolic acid and valganciclovir were stopped owing to neutropenia. The patient was administered granulocyte colony-stimulating factor, and the neutrophil count increased to 3.8 x 10(9)/L (leucocyte count to 5.8 x 10(9)/L). The kidney functions did not deteriorate in either patient, and the patients' kidney functions were similar to baseline levels 12 months after surgery.. We conclude that granulocyte colony-stimulating factor can be used safely and effectively in renal transplant patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus Infections; Filgrastim; Ganciclovir; Granulocyte Colony-Stimulating Factor; Humans; Kidney Transplantation; Male; Neutropenia; Recombinant Proteins; Treatment Outcome; Valacyclovir; Valganciclovir; Valine

Mycophenolate mofetil (MMF) is a drug which decreases the frequency of renal transplantation rejection. However, cytomegalovirus infections are a common feature of this treatment leading the physicians to prescribe antiviral prophylactic drugs like valacyclovir. During this association, neutropenia occur and the cause of this adverse effect is difficult to define. This report presents a case of neutropenia in a woman treated with MMF and valacyclovir. As the duration of the valacyclovir treatment exactly corresponds to the neutropenia duration, and the mycophenolate trough levels increased with the neutrophil count, the responsibility of this neutropenia was ascribed to valacyclovir. However, an examination of the literature for cases of neutropenia led to the suspicion of an interaction between MMF and valacyclovir. Mycophenolate may increase intracellular concentrations of valacyclovir up to haematotoxic levels. This mechanism may explain the interaction and further research is needed to confirm this interaction.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Drug Interactions; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Neutropenia; Valacyclovir; Valine

The extent and duration of neutropenia and the characteristics of the underlying disease are determinant factors for the prognosis of febrile syndromes. Despite the fact that traditionally the peripheral blood stem cell transplantation (PBSCT) were considered to cause high risk neutropenia, in all probability the neutropenia observed in the PBSCT in some solid tumours could be considered moderate risk. Febrile episodes in patients with these characteristics were evaluated.. We prospectively analysed 132 autologus PBSCT in patients with breast cancer (1994-1999). Conditioning regime: STAMP V. Antibacterial prophylaxis: ofloxacin (400 mg/12 hrs PO). Classification of the febrile syndrome: bacteremia, microbiologically documented infection withut bacteremia, clinical infection and a fever of unknown origin.. 122 patients had a fever (92%), mean age: 45 years (range: 27-61). There were 32 (26%) bacteremias, 13 (11%) microbiologically documented infections without bacteremia and 54 (44%) clinical infections. The mean number of days with a neutrophil count of <1x109/1 was 14 (range: 11-20). In the 74 patients (61%) that had a granulocyte colony stimulating factor (G-CSF), the mean number of days to reach a 0,5x109/I neutrophil count (7,6) and the average number of days in hospital (26) were significantly less. There was a main infectious point in 80 patients (65%): the most frequent being oropharynx in 33 cases (46%) and digestive in 29 cases (41%). 48 gram negative (GN) 29 gram positive (GP) bacteria were isolated (71% of the GN's were resistant to ofloxacin). Between 1997-1999 the GN/GP ratio was 2,3. There were no deaths related to the infection.. Given the excellent evolution of our patients we can consider their neutropenia to be moderate or low risk, and they are a long way from the death rates caused by infections published by other types of hemopoietic transplants. The predominance of GN over the last few years and their limited sensitivity to quinolones means that their prophylactic use in these patients should be reconsidered.

Topics: Acyclovir; Adult; Anti-Infective Agents; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Bacteremia; Bacterial Infections; Breast Neoplasms; Carboplatin; Combined Modality Therapy; Cyclophosphamide; Drug Resistance; Female; Fever; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Incidence; Infection Control; Middle Aged; Neutropenia; Ofloxacin; Premedication; Prospective Studies; Transplantation Conditioning; Trimethoprim, Sulfamethoxazole Drug Combination

Purine analogs and alkylating agents are the most active drugs in the treatment of patients with chronic lymphocytic leukemia (CLL). Although fludarabine is the most widely tested purine analog in CLL, myelosuppression has limited its use in combination chemotherapy regimens. Because pentostatin (Nipent; SuperGen, San Ramon, CA), a related purine analog with proven activity in CLL, has less myelosuppression, we postulated that it would prove advantageous and could be more readily combined with alkylating agents. We are conducting a phase I/II trial of combination chemotherapy with pentostatin and cyclophosphamide for previously treated patients with CLL. Patients need to have Rai high-risk disease or "active" intermediate-risk disease. The treatment regimen consists of a fixed dose of pentostatin (4 mg/m2) combined with an increasing dose of cyclophosphamide. We plan to treat cohorts of three patients each at cyclophosphamide dose levels of 600, 900, 1,200, 1,500, and 2,000 mg/m2. Cycles will be repeated every 21 days. If unacceptable toxicity is encountered at one dose level, then three additional patients (total of six patients) will be accrued to that dose level before further dose escalations will be permitted. A second instance of unacceptable toxicity will close that dose level and identify the preceding level as the phase II dose. Additional patients will be accrued to the phase II dose level to better assess response. Supportive measures include the use of granulocyte colony-stimulating factor (5 microg/kg/d) to limit neutropenia. Sulfamethoxazole/trimethoprim will be given as prophylaxis against Pneumocystis carinii pneumonia and acyclovir will be administered as prophylaxis for herpes zoster. Response will be assessed according to standard criteria, and flow cytometry and fluorescent in situ hybridization will be used to assess for minimal residual disease in patients with trisomy 12.

Topics: Acyclovir; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chemoprevention; Chromosomes, Human, Pair 12; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Herpes Zoster; Humans; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Neutropenia; Patient Selection; Pentostatin; Pneumonia, Pneumocystis; Remission Induction; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Trisomy

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Child; Chronic Disease; Herpes Labialis; Humans; Leukocyte Count; Male; Neutropenia; Neutrophils; Patient Selection; Platelet Count; Practice Guidelines as Topic; Thrombocytopenia; Time Factors

Mucositis is a common complication following chemotherapy. Clinical findings similar to herpetic infection are observed in some patients. Acyclovir administered in addition to empirical, antibiotic treatment improves the course of mucositis, and can also bring down the temperature. The aim of our study was to define the etiological influence of herpetic infection on the course of febrile neutropenia in patients with mucositis. A total of 34 patients with febrile neutropenia were divided into 2 groups: 15 with typical herpetic eruption, and 19 with non-specific mucositis. Both groups received 5-10 mg/kg acyclovir every eight hours together with empiric antibiotic treatment. The effect of acyclovir was studied, and results compared in the two patient groups. Body temperatures decreased in both groups, clinical symptoms, however, disappeared more slowly in the group with non-specific mucositis. The beneficial effect of acyclovir treatment was particularly well expressed in seropositive patients. In this group of patients, herpetic infections may recur under further chemotherapy. Thus, it would be useful to administer acyclovir to them prophylactically during risk periods.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Diagnosis, Differential; Female; Fever of Unknown Origin; Hematologic Neoplasms; Herpes Simplex; Humans; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Stomatitis; Virus Activation

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anti-Infective Agents; Antiviral Agents; Ceftazidime; Cephalosporins; Granulocyte Colony-Stimulating Factor; Humans; Male; Neutropenia; Pyrimethamine; Sulfadiazine; Trimethoprim, Sulfamethoxazole Drug Combination

A 36-year-old Japanese man who received an unrelated bone marrow transplant (BMT) developed severe mucocutaneous infection with herpes simplex virus (HSV) type 1 during oral acyclovir prophylaxis. The lesions progressed despite treatment with intravenous acyclovir and vidarabine. The HSV isolates were sensitive acyclovir, vidarabine and foscarnet in vitro, but peripheral CD3- or CD19-positive cells were barely detectable even 4 months after transplant. A 12-day course of treatment with foscarnet led to a rapid improvement. Foscarnet therapy should be considered for all severe HSV infections following BMT, regardless of whether or not the HSV isolates are sensitive to acyclovir.

Topics: Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Drug Resistance, Microbial; Foscarnet; Herpes Labialis; Humans; Leukemia, Myeloid, Accelerated Phase; Male; Neutropenia; Simplexvirus; Stomatitis, Herpetic; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation

A newborn infant whose condition was diagnosed as herpes simplex encephalitis and who had subsequent recurrences of skin disease had repeated episodes of neutropenia while receiving therapy with intravenous (30 mg/[kg.d]) or oral (30 mg/]kg.d]) acyclovir. The neutropenia did not recur when the dosage of oral acyclovir was reduced to 10 mg/(kg.d). This case represents the first well-documented report of acyclovir-induced neutropenia.

Topics: Acyclovir; Encephalitis, Viral; Female; Follow-Up Studies; Herpesvirus 2, Human; Humans; Infant, Newborn; Magnetic Resonance Imaging; Neutropenia

Topics: Acyclovir; Adult; Bone Marrow Transplantation; Female; Granulocytes; Herpes Simplex; Humans; Leukocyte Count; Male; Neutropenia

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Agranulocytosis; Bacterial Infections; Breast Neoplasms; Candidiasis; Female; Herpes Zoster; Hodgkin Disease; Humans; Immunocompromised Host; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Neutropenia

The incidence of mucocutaneous herpes simplex virus infection confirmed by culture and occurring during febrile neutropenic episodes was determined in 43 patients with haematological malignancy. The outcome of 72 episodes of neutropenic fever was determined and correlated with the presence or absence of herpes simplex virus (HSV) infection. Twenty four patients had mucocutaneous HSV infection during at least one episode. In 24 episodes in which HSV was isolated only 12.5% of fevers responded to antibiotics and 75% of fevers were otherwise unexplained. Conversely, in 48 episodes of neutropenic fever in which HSV was not isolated 67% of fevers responded to antibiotics and only 8.3% were unexplained. The difference in incidence of antibiotic resistant fever in the two groups was significant. There was, therefore, a strong association between mucocutaneous HSV infection and antibiotic resistant fever in immunosuppressed neutropenic patients. As most HSV infections are the result of virus reactivation, establishing the HSV serological state of patients would identify those at risk of infection and hence those in whom the prophylactic use of acyclovir would be indicated.

Topics: Acyclovir; Agranulocytosis; Drug Resistance, Microbial; Fever; Herpes Simplex; Humans; Leukemia; Neutropenia; Virus Activation

Topics: Acyclovir; Agranulocytosis; Antibodies, Viral; Central Nervous System Diseases; Chickenpox; Child; Herpesvirus 3, Human; Humans; Leukopenia; Liver Diseases; Male; Neutropenia

To determine if the combination of ganciclovir and intravenous cytomegalovirus immunoglobulin is effective in patients with cytomegalovirus pneumonia after bone marrow transplant.. Consecutive entry trial with treatment for a minimum of 14 days.. Consecutive sample of 25 patients with bone marrow transplants and cytomegalovirus pneumonia after transplant proven by open lung biopsy or bronchoalveolar lavage. Patients with abnormal renal function or concomitant infectious causes of pneumonia, or who were respirator-dependent at diagnosis, were not eligible.. Induction treatment consisted of ganciclovir, 2.5 mg/kg body weight every 8 hours for 14 days, and cytomegalovirus immunoglobulin, 400 mg/kg on days 1, 2, and 7 and 200 mg/kg on day 14. Ganciclovir dosage was adjusted for renal function. Patients who were improved but still symptomatic after 14 days were given maintenance treatment consisting of ganciclovir, 5 mg/kg once daily for an additional 14 days, and immunoglobulin, 200 mg/kg on day 21. Patients with clinical deterioration continued to receive induction doses. Ganciclovir therapy was discontinued if the neutrophil count fell below 500 X 10(6)/L for 2 consecutive days.. Serial tests of renal and liver function, blood counts, and viral cultures of blood, throat, and urine were obtained 3 times a week. Thirteen of twenty-five (52%) patients (95% CI, 31 to 72) survived the initial episode of pneumonia. Viral excretion ceased in 17 of 23 (74%) patients treated more than 96 hours. Proven recurrences of pneumonia occurred in 3 patients and possible recurrences in 2 after treatment was stopped. Three patients developed neutropenia during induction therapy and 6 patients during maintenance therapy.. Survival of 13 (52%) of 25 patients from the initial episode of cytomegalovirus pneumonia with the regimen of ganciclovir and cytomegalovirus immunoglobulin is significantly better (P less than 0.001) than the survival of 13 of 89 (15%) patients using previous antiviral regimens.

Topics: Acyclovir; Adolescent; Adult; Antibodies, Viral; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunization, Passive; Male; Middle Aged; Neutropenia; Pneumonia, Viral; Postoperative Complications; Prospective Studies; Pulmonary Fibrosis

Of 760 AIDS patients seen at San Francisco General Hospital in 1986, 5.7 per cent had retinitis and 2.2 per cent had gastrointestinal disease caused by cytomegalovirus. We reviewed the records of 44 patients treated with ganciclovir for culture-confirmed cytomegalovirus retinal (31 patients) or gastrointestinal disease (17 patients) or both (four patients) in 1986. Retinitis stabilized or improved during initial treatment with ganciclovir in 22 of 27 (81.5 per cent) patients. Following a median 10-day induction course, 16 patients with retinitis continued to have serial ophthalmologic assessments: eight patients were maintained on treatment and eight had maintenance treatment deferred. Before treatment, the two groups were comparable in age, Karnofsky scores, hematologic assessment, visual acuity, and history with respect to Pneumocystis carinii pneumonia. Retinitis did not progress for a median 53.8 days in the immediate maintenance group compared to 18.8 days for the deferred maintenance group (p = 0.01). In 17 patients with CMV gastrointestinal disease, nine of 14 (64 per cent) had resolution of pain and eight of 11 (73 per cent) had resolution of diarrhea when treated initially with ganciclovir. In both retinitis and gastrointestinal disease patients, ganciclovir decreased recovery of CMV from urine and blood markedly. Ganciclovir also caused a decrease in mean absolute neutrophil counts to about half of baseline values; decreases in mean platelet count and hemoglobin were also noted but were less than 25 per cent. Neutropenia severe enough to require dose adjustment (less than 800 cells/microliters) occurred in 31 per cent of patients receiving maintenance ganciclovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases; Humans; Neutropenia; Opportunistic Infections; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Agranulocytosis; Anti-Infective Agents; Humans; Leukocyte Count; Male; Neutropenia

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Male; Middle Aged; Neutropenia; Retina; Retinal Diseases; Vision, Ocular

A 15-month prospective study of 109 patients with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) was conducted. Cytomegalovirus (CMV) retinitis developed in 18 of these patients; they were treated with ganciclovir. Five other patients with CMV retinitis who were not part of the prospective study were also treated with ganciclovir. CMV retinitis frequently involved the peripheral retina. All 23 patients treated with ganciclovir showed clinical regression of retinitis, although breakthrough recurrence of CMV retinitis occurred in seven patients (30.4%) while on maintenance therapy with ganciclovir. During treatment, neutropenia (less than 1000 leukocytes/mm3) developed in three patients (13%). Ganciclovir is an effective means of therapy for CMV retinitis, but it must be given chronically to prevent reactivation. Breakthrough recurrences while on maintenance therapy are not uncommon, but can be successfully treated with more aggressive treatment with ganciclovir. In addition, the prognosis for survival of AIDS patients being treated with ganciclovir is improved when compared with that of untreated patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Neutropenia; Prospective Studies; Recurrence; Retinitis

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Ganciclovir; Humans; Male; Methylprednisolone; Neutropenia; Pneumonia, Viral; Postoperative Complications

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kinetics; Male; Middle Aged; Neutropenia; Pneumonia; Retinitis; Time Factors

Cytomegalovirus (CMV) retinopathy, a relentlessly progressive disease that results in permanent blindness, is the most common opportunistic infection of the eye in patients with the acquired immunodeficiency syndrome. Twenty patients with the acquired immunodeficiency syndrome with CMV retinopathy were treated with a new, experimental, antiviral drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (BW B759U), in dosages ranging from 5.0 to 14.0 mg/kg/d for a ten- to 20-day course. In 19 patients (95%), treatment halted the progression of infection and decreased retinal opacification, hemorrhage, and vasculitis. Vision remained stable in most cases. Six patients received no additional treatment. Fourteen patients received continued treatment with a lower maintenance dosage. Retinal disease reactivated in all patients who did not receive maintenance therapy immediately after initial treatment, indicating persistence of live virus despite drug therapy. Reactivation of disease also developed in four (40%) of ten patients receiving continuous, uninterrupted maintenance therapy for longer than three weeks. Reversible neutropenia, requiring cessation of treatment, developed in five (25%) of 20 patients on initial treatment and five (36%) of 14 patients receiving maintenance therapy. Rhegmatogenous retinal detachment was a late complication in four patients. BW B759U appears to be useful in the management of CMV retinopathy by reducing or delaying visual loss.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Drug Evaluation; Ganciclovir; Humans; Male; Middle Aged; Neutropenia; Retinal Diseases; Visual Acuity

Considerable progress has been made in the supportive care of patients undergoing cancer therapy. This progress has been associated with the improved survival of some patients. However, infection continues to be the major fatal complication in cancer. patients. The response of granulocytopenic patients with infections to some of the current available antibiotics is suboptimal. Since neutropenia is common during cancer treatment, there is a continual risk of infection in cancer patients; thus it is important for medical oncologists to become aware of these complications and their management. The most frequent types of acute infections, their clinical manifestations, and available antibiotic therapies were reviewed.

Topics: Acyclovir; Anti-Bacterial Agents; Bacterial Infections; Fever; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Neoplasms; Neutropenia; Vidarabine; Virus Diseases

Ten marrow transplant recipients with biopsy-proven cytomegalovirus pneumonia were treated with the acyclic nucleoside analog 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (BW B759U). Viruria and viremia ceased after 4 days of treatment in all patients with cultures initially positive from these sites. Cytomegalovirus was eliminated from respiratory secretions after a median of 8 days. Despite this antiviral effect, only one patient survived the pneumonia. Quantitative cultures of lung tissue before and after treatment confirmed that therapy with BW B759U was associated with substantial antiviral activity, with a mean decrease in viral titers of more than 99.99% after treatment. Neutropenia developed in three patients when mean peak and trough plasma levels exceeded 50 and 10 mu mol/L, respectively, but no other toxicity was seen. BW B759U is the first antiviral agent showing consistent activity against cytomegalovirus in vivo, and it should be evaluated in the earlier management of cytomegalovirus infections after marrow transplantation and in serious cytomegalovirus infections in other immunocompromised patients.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Child, Preschool; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kidney Diseases; Lung; Male; Neutropenia; Pneumonia, Viral; Postoperative Complications; Tissue Distribution