B. Salzberger

OUTCOMES OF NOSOCOMIAL BLOODSTREAM INFECTIONS IN ADULT NEUTROPENIC PATIENTS: A PROSPECTIVE COHORT AND MATCHED CASE-CONTROL STUDY

OBJECTIVE To examine the clinical and epidemiologic features, excess length of stay, extra costs, and mortality attributable to bloodstream infection (BSI) in neutropenic patients with hematologic malignancies. DESIGN Prospective cohort and matched case-control study. PATIENTS All adult neutropenic patients with hematologic malignancies admitted to Cologne University Hospital between May 1, 1997, and April 30, 1998, were prospectively observed. Case-patients were defined as patients with nosocomial BSI; control-patients were selected among patients without BSI. RESULTS During the study period, the BSI rate in neutropenic patients was 14.3 per 100 neutropenic episodes. Eighty-four case-patients were included. Matching was successful for 96% of the cohort; 81 matched pairs were studied. The mean total length of stay was significantly longer for patients with BSI than for control-patients (37 vs 29 days; P = .002). Extra costs attributable to the infection averaged 3,200 dollars (U.S.) per patient. The crude mortality rates of case-patients and control-patients were 16% and 4%, respectively (P = .013), with an attributable mortality of 12% (odds ratio, 11). Eighty-seven percent of patients met the criteria for sepsis according to the American College of Chest Physicians/Society of Critical Care Medicine. Severe sepsis or septic shock occurred in 13% of patients and was correlated with mortality (55% vs 10% in patients without severe sepsis or septic shock; P = .01). CONCLUSIONS Nosocomial BSI in neutropenic patients is significantly associated with an excess length of hospital stay, extra costs, and excess mortality. Severe sepsis and septic shock are closely correlated with an adverse outcome.

Seroprevalence and disease association of antineutrophil cytoplasmic autoantibodies and antigens in HIV infection.

SummaryThis prospective study was designed to determine the role of antineutrophil cytoplasmic autoantibodies (ANCA) in HIV-infected patients. Immunofluorescence tests (IFT) and enzyme-linked immunosorbent assays (ELISA) were applied to sera of 199 consecutive outpatients. In the IFT 20% were positive. An atypical ANCA pattern was demonstrated in 67% of these, 33% revealed a perinuclear staining (pANCA). Specific ELISA revealed proteinase 3 (n=2), myeloperoxidase (n=1), lysozyme (n=2), lactoferrin (n=1), cathepsin G (n=1), and human leukocyte elastase (HLE, n=6). The target antigen remained unidentified in 26 patients. Perinuclear ANCA-positive patients showed atypical antigens in eight of 13 cases; all six patients with anti-HLE revealed a pANCA pattern. The antigens of atypical ANCA-positive patients remained unidentified in 21 of 26 (81%) cases. No signs of vasculitis were present in the ANCA-positive patients. ANCA are frequently found in the sera of HIV-positive patients. They bind to a variety of antigens. No correlation was found between ANCA positivity and autoimmune or opportunistic diseases.

Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy

Background:Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV–infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort.Patients and Methods:All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993–1996 was classified as pre–HAART, the period from 1997–1999 as the HAART era. Survival was analyzed with a Cox–proportional hazard model.Results:From a total of 1,279 HIV–infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre–HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre–HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow–up in the HAART era. The only risk factors influencing survival were CD4–cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities.Conclusion:A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era.

Resting energy expenditure, weight loss, and altered body composition in HIV infection

Failure to downregulate resting energy expenditure (REE) as an adaption to anorexia or malabsorption is often stated as the major cause of weight loss in individuals with AIDS. In a prospective study, REE was compared with weight changes in HIV-infected patients. The impact of altered body composition on REE was reassessed by critical review of the literature. Patients were 65 male HIV-infected patients, 28 with recent weight loss (WL), and 37 who were weight stable (WS); 50/65 patients had AIDS, and 29/65 had acute infections; 29 male healthy persons served as controls. Indirect calorimetry, prospective intake protocol, and bioelectrical impedance analysis were performed. Absolute REE was lower in WL patients than in controls (1459 +/- 309 versus 1711 +/- 151 kcal/d, p < 0.001) and in WS patients (1625 +/- 402 kcal/d, p < 0.05). REE/kg body cell mass (BCM) was higher in WL and WS than in controls (both p < 0.01) due to lower BCM in both patient groups (p < 0.001). REE (%Harris-Benedict) was not different among the three groups. Weight changes around the measurement were not correlated to REE (r2 = 0.0008, p = 0.82). REE was independent of diarrhea, acute infection, fever, or caloric intake. REE had a stronger correlation to body weight and to Harris-Benedicts prediction than to fat-free mass or BCM. REE explains < 1% of weight changes. Many patients can downregulate REE as an adaption to anorexia and/or malabsorption. Higher REE/kg BCM does not signify hypermetabolism at the cellular level but can be explained by the maintenance of energy-consuming visceral tissue within the BCM during BCM loss.

Detection of Isospora belli by polymerase chain reaction using primers based on small-subunit ribosomal RNA sequences.

Abstract The aim of the present study was to use small-subunit (SSU)-rRNA sequences of Isospora belli to design specific primer pairs and a hybridization probe for the detection of Isospora belli in human samples by PCR and Southern blot hybridization. PCR amplification with the primer pairs produced correct DNA fragments with target DNA from samples of Isospora belli-infected patients and from cloned SSU-rRNA of Isospora belli. The nature of the PCR products was confirmed by Southern blot hybridization. No amplification was seen with template DNA extracted from other parasites. Although Isospora belli infections can be easily diagnosed using light microscopy, molecular-based techniques may prove useful as an additional diagnostic tool.

Taxonomic position of the human intestinal protozoan parasite Isospora belli as based on ribosomal RNA sequences

Abstract The taxonomic positions of Isospora belli and other members of the genus Isospora are controversial. We determined the small-subunit ribosomal RNA of I. belli and used this sequence in combination with other coccidian RNA sequences for analysis of the taxonomic position of I. belli. The phylogenetic trees we obtained provide molecular evidence for three clades within a monophyletic group that represents the suborder Eimeriina. The clade containing I. belli consists of tissue-cyst-forming coccidia (Toxoplasma and Neospora) and members of the genus Isospora (I. ohioensis, I. suis, I. belli). The second clade, representing a sister clade of that containing the Isospora species, contains members of the genus Sarcocystis. The third one consists of members of the family Eimeriidae, including Eimeria and Cyclospora species. This shows that although I. belli as well as other members of the genus Isospora belong to the suborder Eimeriina, the family to which they belong is not Eimeriidae but rather Sarcocystidae. We suggest that the genus Isospora should be removed from the family Eimeriidae and placed into the family Sarcocystidae within the suborder Eimeriina.

Body Weight Changes With Protease Inhibitor Treatment in Undernourished HIV-Infected Patients

Effective reduction of HIV replication by protease inhibitor (PI) treatment was expected to reverse some of the weight loss associated with HIV infection. Body weight changes in undernourished HIV-infected patients starting PI treatment were compared to its virologic and immunologic effects. This was designed as a retrospective study using prospectively collected weight data; the setting was the HIV outpatient department of a university hospital. Among 223 consecutive HIV-positive patients starting treatment with PI February 1996 to September 1997, 63 undernourished patients were evaluable. The main outcome measures were weight trend, calculated by linear regression of a patients weight versus time, and its change from a 4-14-wk baseline period to the first 14 wk, and 28 wk, after treatment. In our results, weight trend remained unchanged (baseline, +0.4 +/- 4.0 kg/100 d; 14 wk, +0.7 +/- 4.1 kg/100 d, and 28 wk, +1.0 +/- 3.4 kg/100 d, n.s.). Reduction of viremia and increase in CD4 cell count were unrelated to weight trends. Treatment with PI did not result in an improved weight trend. Altered body composition with PI treatment, as observed in other studies, does not seem to result in body weight changes. Drug side effects may have counteracted any positive effects. The metabolic and nutritional impact of effective antiviral treatment merits further study.

Raynaud's phenomenon and acral necrosis after chemotherapy for AIDS-related Kaposi's sarcoma

Raynauds phenomenon is a common vascular side effect of chemotherapy drug regimens. Chemotherapy-induced Raynauds phenomenon leading to acral gangrene has rarely been reported. In this report, one patient who developed gangrene after bleomycin and vincristine/vinblastine chemotherapy for AIDS-related Kaposis sarcoma and another HIV-infected patient who exhibited symptoms of severe Raynauds phenomenon related to the same regimen are presented. Because the combination of bleomycin and vinca alkaloids is commonly used for the treatment of AIDS-related Kaposis sarcoma, clinicians should be aware of the risk of provoking acral necrosis in patients who develop Raynauds phenomenon under chemotherapy. The literature is reviewed, and clinical symptoms, pathophysiology, and treatment options are discussed.

Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever.

Abstract A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus tobramycin 5 mg/kg in comparison to cefotaxime 2 g t.i.d. plus tobramycin 5 mg/kg qd in the treatment of neutropenic fever. In cases of fever ≥38.5  °C and a neutrophil count below 1000/μl, patients with hematological malignancies were assigned to ceftriaxone or cefotaxime, each with tobramycin. The primary endpoint was defined as defervescence <37.5  °C on day 4–6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 25 and toxicity. There were 160 episodes of 114 patients included. Fever of unknown origin accounted for 79 episodes (51%), microbiologically defined infection for 36 (23%), clinically defined infection for 27 (17%), and both clinically and microbiologically defined infection for 14 episodes (9%). On an intent-to-treat basis 156 episodes could be evaluated for the primary endpoint. Ceftriaxone plus tobramycin and cefotaxime plus tobramycin resulted in a primary response in 46.9% and 45.3%, respectively. Overall response was achieved on study day 25 in 87.7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever.

Intestinal microsporidiosis with Septata intestinalis in a patient with AIDS—response to albendazole

Microsporidiosis is a common finding in HIV-infected patients who have diarrhoea. The species most commonly causing gastrointestinal disease is Enterocytozoon bieneusi. Recently Septata intestinalis has been described as a cause of diarrhoea and disseminated infection in patients with AIDS. A 44-year-old homosexual man with severe immunodeficiency (CD4 cell count 40/microliters) had a history of watery diarrhoea for 2 weeks. Microsporidian spores measuring 1.2 to 1.5 x 2.5 to 3.0 microns were found in stool samples. Electron microscopy of duodenal biopsies confirmed the diagnosis of intestinal microsporidiosis and showed parasitophorous vacuoles with the typical ultrastructure of S. intestinalis. The patient was treated with albendazole (400 mg twice daily) and became asymptomatic within 4 days. No spores could be detected in stool samples after a treatment period of 14 days. About 25 infections with S. intestinalis have been reported to date, and the case presented here is the first in a German patient.