Prophylactic Pretransplant Ganciclovir to Reduce Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation.

OBJECTIVE/BACKGROUND: Cytomegalovirus (CMV) reactivation remains a serious complication after allogeneic hematopoietic cell transplantation (HCT) occurring in approximately 60-70% of CMV-seropositive HCT recipients. CMV reactivation leads to adverse outcomes including end-organ damage, graft-versus-host disease, and graft failure. METHODS: Ganciclovir was administered pretransplant at 5 mg/kg twice daily intravenously from the start of conditioning to Day T-2 to CMV-seropositive patients receiving their first allogeneic HCT. CMV DNA was monitored weekly until at least Day 100 posttransplant. RESULTS: A total of 109 consecutive patients were treated, median age 57 (range 20-73) years. Of these, 36 (33%) patients had a CMV reactivation within the first 105 days posttransplant with a median time of reactivation of 52.5 (range 36-104) days posttransplant. The cumulative incidence of CMV reactivation at Day 105 posttransplant was 33.1% (95% confidence interval: 24.4-42.0). One patient developed CMV disease. CONCLUSION: The use of pretransplant ganciclovir was associated with low incidence of CMV reactivation and disease. These data suggest that pretransplant ganciclovir with preemptive therapy for viral reactivation may be a useful strategy to reduce CMV reactivation. Future prospective trials are needed to compare strategies for CMV prophylaxis.

Case report: Anaerobiospirillum prosthetic joint infection in a heart transplant recipient.

BACKGROUND: We report a case of prosthetic hip joint infection in a heart transplant recipient due to Anaerobiospirillum succiniciproducens, a genus of spiral-shaped curved anaerobic gram-negative rod which colonizes the gastrointestinal tract of cats and dogs. Invasive infections in humans are rare and typically occur in immunocompromised hosts. CASE PRESENTATION: A 65-year-old male dog breeder with a history of rheumatoid arthritis, bilateral hip arthroplasties, and non-ischemic cardiomyopathy with a heart transplant 10 years ago presented with a three month history of progressive left hip pain and frank purulence on hip aspiration. He underwent irrigation and debridement of the left hip and one-stage revision with hardware exchange. Although gram stain and culture from synovial fluid and intraoperative cultures were initially negative, anaerobic cultures from tissue specimens later grew a spiral-shaped gram-negative rod, identified as Anaerobiospirillum spp. by 16S rRNA gene sequencing. The patient was treated with ceftriaxone 2 g daily for 6 weeks with a good response to treatment. A similar organism was unable to be isolated from culture of 2 of the patient's dogs, however, they were thought to be the most likely source of his infection. CONCLUSION: Anaerobiospirillum spp. should be considered in immunocompromised patients with exposure to dogs or cats who present with bacteremia, gastrointestinal infection, pyomyositis, or prosthetic joint infections, especially in cases of culture-negative or with anaerobic culture growth.

Community-acquired pneumonia: 2012 history, mythology, and science.

Pneumonia remains one of the major disease entities practicing physicians must manage. It is a leading cause of infection-related morbidity and mortality in all age groups, and a leading cause of death in those older than 65 years of age. Despite its frequency and importance, clinical questions have remained in the therapy of community-acquired pneumonia including when to start antibiotics, when to stop them, who to treat, and what agents to use. Answers to these questions have involved historical practice, mythology, and science-sometimes good science, and sometimes better science. How clinical decisions are made for patients with community-acquired pneumonia serves as an illustrative model for other problem areas of medicine and allows for insight as to how clinical decisions have been made and clinical practice established.

Bacterial community-acquired pneumonia in older patients.

Pneumonia in the elderly remains a major source of morbidity and mortality in an age group that is growing in numbers. It remains unclear whether the propensity of older adults to develop community-acquired pneumonia represents an aging of host defenses, secondary effects of comorbid disease, or both. The signs and symptoms of pneumonia in the elderly are more subtle than in younger populations, which may lead to a delay in diagnosis. Although therapy for community-acquired pneumonia in the elderly is the same as for younger populations, mortality is higher, leading to an important role for prevention.

Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial.

BACKGROUND: Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. METHODS: We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. RESULTS: Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. CONCLUSIONS: Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.

Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia.

BACKGROUND: Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B. METHODS: In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point. RESULTS: Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events. CONCLUSIONS: Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.

Triad of acute infusion-related reactions associated with liposomal amphotericin B: analysis of clinical and epidemiological characteristics.

We investigated the clinical characteristics and treatment of patients with a distinctive triad of acute infusion-related reactions (AIRRs) to liposomal amphotericin B (L-AMB) via single-center and multicenter analyses. AIRRs occurred alone or in combination within 1 of 3 symptom complexes: (1) chest pain, dyspnea, and hypoxia; (2) severe abdomen, flank, or leg pain; and (3) flushing and urticaria. The frequency of AIRRs in the single-center analysis increased over time. Most AIRRs (86%) occurred within the first 5 min of infusion. All patients experienced rapid resolution of symptoms after intravenous diphenhydramine was administered. The multicenter analysis demonstrated a mean overall frequency of 20% (range, 0%-100%) of AIRRs among 64 centers. A triad of severe AIRRs to L-AMB may occur in some centers; most of these reactions may be effectively managed by diphenhydramine administration and interruption of L-AMB infusion.

Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial.

BACKGROUND: Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. OBJECTIVE: To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever. DESIGN: Randomized, double-blind multicenter trial. SETTING: Seven U.S. university-affiliated hospitals and one private research center. PATIENTS: Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. INTERVENTIONS: Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. MEASUREMENTS: Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. RESULTS: 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). CONCLUSION: Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.