Body mass repletion during ganciclovir treatment of cytomegalovirus infections in patients with acquired immunodeficiency syndrome

Disseminated cytomegalovirus (CMV) infection is a common complication of acquired immunodeficiency syndrome and contributes significantly to its morbidity and mortality. Ganciclovir, a guanosine analogue, inhibits CMV replication in vitro and in vivo, and its use can stabilize the clinical course of an affected patient. We examined the changes in body composition that occurred in four untreated patients and in eight patients who were treated with ganciclovir for serious CMV infections. Untreated patients lost weight, depleted body cell mass, as determined from total-body potassium measurements in a whole-body counter, lost body fat, as estimated from anthropometric measurements, and had a progressive fall in serum albumin concentration. In contrast, treated patients gained weight, repleted body cell mass and body fat, and increased serum albumin concentration during a three-month follow-up. In this study, it was estimated that ganciclovir therapy resulted in a net energy conservation of 2629 kJ/d. The ability to promote body cell mass repletion may be considered a demonstration of the efficacy of ganciclovir in the treatment of serious CMV infections in patients with acquired immunodeficiency syndrome.     

Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants

STUDY OBJECTIVE: To determine if the combination of ganciclovir and intravenous cytomegalovirus immunoglobulin is effective in patients with cytomegalovirus pneumonia after bone marrow transplant. DESIGN: Consecutive entry trial with treatment for a minimum of 14 days. PATIENTS: 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. INTERVENTIONS: 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. MEASUREMENT and MAIN RESULTS: 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. CONCLUSIONS: 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.     

Safety of oral versus intravenous hydration during induction therapy with intravenous foscarnet in AIDS patients with cytomegalovirus infections

We undertook a study to compare the safety of intravenous (i.v.) versus oral hydration to prevent nephrotoxicity associated with the use of foscarnet for induction therapy of cytomegalovirus (CMV) infection in HIV-infected persons. Patients, given foscarnet at a dose of 90 mg/kg every 12 h, were randomized to receive either i.v. or oral hydration. Thirty-seven patients were given i.v. hydration and 44 were given oral hydration. Median duration of therapy for both groups was 17 days. There was no difference between the 2 groups in either serious adverse events or rise of creatinine to > or = 2.0 mg/dl. However, serum creatinine, while generally remained within normal limits, increased more in patients who received oral hydration after 10 days of therapy (significant only by slope analysis, P < 0.05). Although i.v. hydration provided better protection against nephrotoxicity, oral hydration was relatively safe and convenient provided that creatinine clearance (CrCl) is monitored closely.     

Successful treatment of Epstein-Barr virus-induced transverse myelitis with ganciclovir and cytomegalovirus hyperimmune globulin following unrelated bone marrow transplantation

We report a patient who developed Epstein-Barr virus (EBV)-induced transverse myelitis 19 months after unrelated bone marrow transplantation (BMT). The disease was diagnosed by physical examination, serologic determinations, EBV-specific polymerase chain reaction in peripheral blood lymphocytes and cerebrospinal fluid, and characteristic magnetic resonance imaging scan of the spine. The patient was treated with ganciclovir and cytomegalovirus (CMV) hyperimmune globulin. He gradually improved and recovered completely within 4 weeks. This case suggests that ganciclovir and CMV hyperimmune globulin appear to be effective for the treatment of EBV-induced transverse myelitis in immunocompromised patients following BMT.     

Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.     

Phase I study of combination therapy with intravenous cidofovir and oral ganciclovir for cytomegalovirus retinitis in patients with AIDS.

Ganciclovir and cidofovir, two antiviral agents used in the treatment of cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV replication in vitro. In a phase I study, seven patients with AIDS-related CMV retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks) combined with ganciclovir (1 g orally three times a day). During a median of 5.5 months (range, 1-12 months) of combined therapy, only one patient had retinitis progression, and only two of 28 blood cultures (specimens of which were obtained on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior uveitis [two patients] and hypotony [two patients]) occurred in three of seven patients. The results suggest that combination therapy with intravenous cidofovir and oral ganciclovir (a regimen that does not require indwelling central venous catheter access) might enhance clinical efficacy. Less frequent administration of cidofovir in combination with oral ganciclovir should be prospectively studied to determine if the incidence of treatment-associated toxicity might be reduced.     

Successful treatment of Good syndrome with cytomegalovirus duodenoenteritis using a combination of ganciclovir and immunoglobulin with high anti-cytomegalovirus antibody titer

We describe the case of a 64-year-old woman with Good syndrome who presented with watery diarrhea and abdominal distention caused by cytomegalovirus (CMV) duodenoenteritis. Thymoma and hypogammaglobulinemia were first identified when the patient was 58 years old. She had repeatedly complained of symptoms even after thymectomy. Abdominal radiography revealed multiple air-fluid levels, and computed tomography revealed ascites and dilation of the small intestine. Immunofluorescent staining of specimens obtained by duodenal mucosal biopsy revealed intracellular inclusion bodies of CMV, although serum CMV pp65 antigenemia assays yielded negative results. CMV infection of the small intestine caused mucosal edema resulting in malabsorption. The patient was treated using ganciclovir and an immunoglobulin preparation with a high titer of antibodies against CMV (CMV-Ig), and subsequently made a rapid recovery from abdominal symptoms. When patients with Good syndrome complain of abdominal symptoms, particularly chronic diarrhea, a diagnosis of CMV gastroenteritis should not be excluded, even if negative results are obtained for CMV pp65 antigenemia assays. Combination therapy of ganciclovir and CMV-Ig seems useful for patients with CMV gastroenteritis.     

Severe transient osteoporosis of the hip during pregnancy. Successful treatment with intravenous biphosphonates

A young woman with transient osteoporosis of the hip (TOH) during pregnancy, severe pain, physical disability and marked generalized osteoporosis was treated with intravenous biphosphonates with prompt beneficial effects on both clinical symptoms and bone density. The features of this rare and sometimes underdiagnosed condition are reviewed. Intravenous biphosphonates seem to be an effective therapy for TOH.     

Cytomegalovirus encephalitis in two patients with AIDS receiving ganciclovir for cytomegalovirus retinitis

Cytomegalovirus (CMV) encephalitis has been reported with increasing frequency in patients with AIDS. Nevertheless, the management of CMV-related encephalitis appears to be problematic and data in the literature on the clinical efficacy of ganciclovir therapy is sparse and controversial. We describe two patients with AIDS who developed CMV encephalitis while receiving ganciclovir maintenance therapy for CMV retinitis. Moreover, there was no improvement in neurological status or virological and radiological response during a further induction course of ganciclovir. These observations suggest that the currently recommended therapeutic protocols with ganciclovir are not effective in the prevention and treatment of CMV encephalitis in patients with AIDS.     

更昔洛韦胶囊在造血干细胞移植患者巨细胞病毒血症中的应用

目的 探讨更昔洛韦(ganciclovir,DHPG)胶囊治疗造血干细胞移植(HSCT)后患者巨细胞病毒(CMV)血症的疗效和安全性.方法 选择2006年2月至5月在北京大学血液病研究所行HSCT的30例移植后CMV血症患者进行前瞻性研究.CMV感染预防采用更昔洛韦10 mg/(kg·d),分2次静脉滴注,移植前第9天至移植前第2天,连续8 d.移植后应用定量多聚酶链反应(PCR)定期进行病毒DNA检测,CMV-DNA定量＞6.0×102拷贝/mL或＜1×105拷贝/mL的患者应用更昔洛韦胶囊1 g每日3次治疗.结果 HSCT后发生CMV血症的中位时间为移植后42 d,诊断时CMV-DNA中位数4.626×103拷贝/mL.更昔洛韦胶囊治疗的总有效率为90%,14 d转阴率66.67%,转阴中位时间10 d.4例(13.3%)出现不良事件,程度为轻至中度,表现为血细胞计数减少3例,转氨酶升高1例.结论 更昔洛韦胶囊用于治疗HSCT后CMV血症患者安全有效.     

Pulmonary infections associated with non-tuberculous mycobacteria in immunocompetent patients

A decline in the prevalence of tuberculosis in the developed world over the past several years has been accompanied by an increase in the rate of mycobacterial disease caused by non-tuberculous mycobacteria. However, it is still unclear whether there is a real increase in prevalence or whether non-tuberculous mycobacterial disease is being recognised more frequently by clinicians in a variety of clinical settings, thus enhancing the competence of microbiologists to detect the more unusual and fastidious mycobacteria. The introduction of liquid media for isolation of mycobacteria coupled with more accurate methods for identification have allowed several new species associated with human disease to be recognised. Despite this progress, several issues related to non-tuberculous mycobacterial infections need to be addressed, including the timely and reliable identification of isolates, standardisation and clinical evaluation of susceptibility testing, and capability to distinguish disease-causing isolates from contaminant or saprophytic species. Treatment regimens for non-tuberculous mycobacterial disease are still largely undefined and outcome remains disappointing despite substantial upgrading in laboratory diagnosis and the availability of new antimicrobials. Treatment success is impaired by the long duration of regimens, side-effects, and drug interactions, which prevent patients from full compliance. We discuss the epidemiological features, clinical syndromes, and developments in the investigation, prevention, and treatment of pulmonary non-tuberculous mycobacterial infections.     

Severe hyponatremia in older patients at admission in an internal medicine department

Hyponatremia is common in older people, most often of multifactorial origin, and can be associated with poor clinical outcomes. The aim was to analyze the frequency of severe hyponatremia (sodium concentration below 125 mmol/L), risk factors and mortality association in hospitalized older patients. A retrospective study was performed in older patients (over 65 years) with hyponatremia, diagnosed at admission in an Internal Medicine Department during one year. A control group of 127 older patients without hyponatremia was considered. Statistical analysis of the data gathered was made with SPSS Statistics 20. The main results were: a group of 1060 patients with age superior to 65 years was identified (representing 72.26% of total admissions); incidence of hyponatremia in those patients was 27.55% and severe hyponatremia was 5.94%; diagnosis of hyponatremia was mentioned in the discharge note in 66.67% of cases; mortality was 27.0%, against 16.0% in the control group (p = 0.057, Odds Ratio (OR) = 1.940); drugs were a significant risk factor (p < 0.001), specially thiazide diuretics (p = 0.029, OR = 2.774), angiotensin receptor blockers (ARB) (p = 0.001, OR = 4.097), proton-pump inhibitors (PPI) (p = 0.007, OR = 2.561) and spironolactone (p = 0.011, OR = 4.473); other relevant risk factors were: increased water intake (p = 0.004), tube feeding (p < 0.001), vomiting (p = 0.032, OR = 2.492), cirrhosis (p = 0.008, OR = 10.862) and hyperhidrosis (p = 0.017, OR = 2.542). We conclude that, although this group of patients had a high mortality, hyponatremia is often not investigated and not always mentioned as a diagnosis. Clinicians should have a clear appreciation of the roles that iatrogenic interventions and lapses in nutrition frequently play in upsetting the homeostatic balance in older patients.     

更昔洛韦与还原型谷胱甘肽联合治疗巨细胞病毒肝炎患儿的疗效及其对外周血T淋巴细胞水平的影响

目的 探讨应用更昔洛韦联合还原型谷胱甘肽治疗巨细胞病毒肝炎患儿的疗效及其对外周血T淋巴细胞水平的影响。 方法 2015年1月~2016年1月我院收治的巨细胞病毒肝炎患儿74例,按照随机数字表法分为两组,给予37例对照组患儿还原型谷胱甘肽治疗,37例观察组患儿在对照组治疗的基础上联合应用更昔洛韦抗病毒治疗。采用荧光定量PCR法检测尿CMV DNA,使用EpiceXL型流式细胞仪检测外周血T淋巴细胞亚群。 结果 两组治疗前肝功能指标比较无统计学差异（P>0.05）;经过2~3 w治疗,两组血清ALT、AST、GGT、TBIL水平均恢复正常,单观察组尿CMV DNA阴转时间和肝功能恢复时间均显著短于对照组,并发症发生率也较低;治疗前,两组外周血T淋巴细胞亚群无统计学差异（P>0.05）,经过2~3 w治疗,两组外周血CD3+、CD4+、CD8+细胞和CD4+/CD8+比值均恢复正常。 结论 应用更昔洛韦联合还原型谷胱甘肽治疗巨细胞病毒肝炎患儿能加速肝功能恢复,无不良反应发生。     

Successful ganciclovir treatment of primary cytomegalovirus infection containing the UL97 mutation N510S in an intestinal graft recipient

In solid organ transplantation, human cytomegalovirus (HCMV) is considered to be the most important viral pathogen. We report a case of a CMV R?/D+ small intestine transplant recipient with a primary CMV infection on valganciclovir prophylaxis. Sequencing of the HCMV DNA for drug resistance-associated mutations revealed the UL97 mutation N510S. This mutation has been initially reported to confer ganciclovir resistance. Based on in vitro recombinant phenotyping, this assumption has recently been questioned. Switching the antiviral treatment to an intravenous regimen of ganciclovir eliminated HCMV DNAemia, showing the in vivo efficacy of ganciclovir for the UL97 mutation N510S. Hence, knowledge of drug efficacy is crucial for an adequate choice of antiviral medication, carefully balancing antiviral potency versus the risk of harmful side effects.     

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients

The efficacy and safety of oral valganciclovir was compared to ganciclovir i.v. in pre-emptive treatment of cytomegalovirus (CMV) in T-cell-depleted allogeneic stem cell transplant (allo-SCT) recipients. A therapeutic guideline was developed to allow the safe application of valganciclovir in allo-SCT recipients requiring CMV therapy. In total, 107 consecutive transplant recipients were evaluated. Cytomegalovirus DNA load in plasma was monitored longitudinally; details on antiviral therapy and treatment responses were analyzed retrospectively. Fifty-seven CMV treatment episodes were recorded in 34 patients: 20 with valganciclovir (900 mg twice-daily) and 37 with ganciclovir (5 mg/kg twice-daily). Median CMV DNA load reduction was 0.079 and 0.069 log10 copies/ml/day in the ganciclovir and valganciclovir group, respectively. Good response on CMV DNA load (reduction below 3.0 log10 copies/ml) was observed in 75.7% of ganciclovir and 80.0% of valganciclovir treatment episodes. Severe adverse effects were not observed and CMV-related disease did not occur. However, the percentage of patients receiving erythrocyte transfusion was higher in the group of patients receiving ganciclovir as compared to valganciclovir (41 versus 20%, P=0.116). In conclusion, pre-emptive treatment with valganciclovir and ganciclovir, led to similar reduction of CMV DNA load. Oral valganciclovir is an attractive and safe alternative for pre-emptive CMV treatment in T-cell-depleted allo-SCT recipients.     

Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo-controlled trial in AIDS patients

This phase IIa, randomised, single-blind, placebo-controlled study was conducted to determine the dose of recombinant human granulocyte colony-stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) < or = 1.0 x 10(9)/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n = 14) or one of four lenograstim arms: 150 microg/m2/d (the standard onco-haematology dose, n = 13) or 100 (n = 13), 50 (n = 15), or 25 microg/m2/d (n = 14). In all groups, the planned dose of GCV was 10 mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p = 0.05). At week 3, median ANC (x 10(9)/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 microg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 microg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 microg/m2/d group at weeks 2 (p = 0.05) and 3 (p = 0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50 microg/m2/d is suitable for the treatment of ganciclovir-induced neutropenia and is safe. These results should help the physician choose an optimal and cost-efficient regimen for patients with AIDS-related neutropenia when rHuG-CSF support is indicated.