Ten-year review of Clostridium difficile infection in acute care hospitals in the USA, 2005-2014.

Clostridium difficile infection (CDI) is a major health concern for acute care hospitals because of the increase in the number and severity of cases. Using the Nationwide Inpatient Sample database, a 10-year review was performed on the trends in incidence, mortality, and hospital charges for CDI patients in acute care hospitals during 2005-2014. The review found increased CDI incidence and hospital charges, but decreased mortality during the 10-year study period.

Pulmonary aspergillosis and invasive disease in AIDS: review of 342 cases.

Aspergillosis is an infrequent but commonly fatal infection among HIV-infected individuals. We review 342 cases of pulmonary Aspergillus infection that have been reported among HIV-infected patients, with a focus on invasive disease. Invasive pulmonary aspergillosis usually occurs among patients with <50 CD4 cells/mm3. Major predisposing conditions include neutropenia and steroid treatment. Fever, cough, and dyspnea are each present in >60% of the cases. BAL is often suggestive, but biopsy specimens are necessary for definite diagnosis. Amphotericin B is the mainstay of treatment and mortality is > 80%. Avoiding neutropenia and judicious use of steroids may be helpful in prevention. Aggressive diagnostic approach, early initiation of treatment, adequate dosing of antifungals, and close follow-up may improve the currently dismal prognosis.

Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease.

BACKGROUND: Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant increases in CD4 T-helper lymphocyte counts. The main side-effects of the protease inhibitors currently in use include gastrointestinal disturbances, paraesthesias, hyperbilirubinaemia, and nephrolithiasis. The increasing use of these agents in patients with advanced HIV-1 infection and CD4 counts of less than 50 cells/microL may be associated with unforeseen adverse effects not observed in earlier studies of patients with higher CD4 counts. METHODS: Five HIV-infected patients with baseline CD4 lymphocyte counts of less than 50 cells/mL were admitted to the Beth Israel Deaconess Medical Center (Boston, MA, USA) with high fever (> 39 degrees C), leucocytosis, and evidence of lymph-node enlargement within 1-3 weeks of starting indinavir therapy. Informed consent was obtained for studies that entailed CD4 lymphocyte counts, immunophenotyping, isolator blood cultures, and radiological scans. Biopsy samples of cervical, paratracheal, or mesenteric lymph nodes were taken for culture and pathology in four patients. FINDINGS: Lymph-node biopsy samples showed that focal lymphadenitis after initiation of indinavir resulted from unsuspected local or disseminated Mycobacterium avium complex (MAC) infection. The prominent inflammatory response to previously subclinical MAC infection was associated with leucocytosis in all patients and with an increase in the absolute lymphocyte counts in four patients. Three patients with follow-up CD4 counts showed two-fold to 19-fold increases after 1-3 weeks of indinavir therapy. Immunophenotyping after therapy in two patients showed that more than 90% of the CD4 cells were of the memory phenotype. INTERPRETATION: The initiation of indinavir therapy in patients with CD4 counts of less than 50 cells/mL and subclinical MAC infection may be associated with a severe illness, consisting of fever (> 39 degrees C), leucocytosis, and lymphadenitis (cervical, thoracic, or abdominal). The intense inflammatory reactions that make admission to hospital necessary may be secondary to significant numbers of functionally competent immune cells becoming available to respond to a heavy mycobacterial burden. Prophylaxis or screening for subclinical MAC infection, or both, should therefore be done before the beginning of protease-inhibitor therapy in patients with advanced HIV infection.

Two regions of the herpes simplex virus type 1 UL42 protein are required for its functional interaction with the viral DNA polymerase.

Two essential gene products of herpes simplex virus type 1, the viral DNA polymerase (pol) and UL42, its accessory protein, physically and functionally interact to form the core of the viral DNA replication complex. Understanding this essential interaction would provide a basis from which to develop novel anti-herpesvirus agents. We previously have shown that when coexpressed in an in vitro transcription-translation system, UL42 stimulates pol activity (M. L. Gallo, D. I. Dorsky, C. S. Crumpacker, and D. S. Parris, J. Virol. 63:5023-5029, 1989). By analyzing various insertion, deletion, and frameshift mutations of UL42 in this system, we found the C-terminal 149 amino acids to be dispensable for the ability of the protein to stimulate pol activity. In addition, two distinct internal regions of UL42 were found to be required for pol stimulation. Regions I and II were defined to lie between amino acid residues 129 and 163 and between residues 202 and 337, respectively. When physical association was examined with antibody to UL42, pol was found to coimmunoprecipitate to the same level when expressed with a UL42 mutant protein lacking region I as that with wild-type UL42. Thus, mere physical association is insufficient for stimulation of pol activity. Deletion of region II reduced or eliminated coimmunoprecipitation with pol. Interestingly, an antibody to pol specific for residues 1216 to 1224 coimmunoprecipitated UL42 when both proteins were synthesized in a baculovirus expression system but not in rabbit reticulocyte lysates. These results indicate that (i) at least a portion of the region recognized by the pol antiserum may be accessible in the pol-UL42 heterodimer and (ii) immunoprecipitation results for products made in different expression systems may vary. Thus, at least two distinct regions of UL42 are essential for functional interaction with pol. Moreover, these results point to a UL42 region I function other than physical association with pol.

Invasive aspergillosis in patients with AIDS.

Invasive aspergillosis is a rare complication of AIDS. We discuss the cases of 18 patients with AIDS and invasive aspergillosis who were identified at our institution and 19 patients who are described in the literature. Twenty-one patients were either homosexual or bisexual, eight were intravenous drug users, three were hemophiliacs, two attributed their disease to a heterosexual contact, and one was a transfusion recipient; risk factors for AIDS were unknown for two patients. Twenty-eight of the 37 patients had pulmonary aspergillosis; for 18 of these 28, the lung was the sole site of disease. Aspergillosis involved the brain in 12 cases, the heart in five cases, and the kidney, sinuses, or skin in six other cases. Eleven patients had multiple sites of disease, and eight patients had extrapulmonary disease alone. Possible risk factors for aspergillosis included leukopenia (7 patients, of whom 5 were also neutropenic) and use of corticosteroids (8 patients), alcohol (6 patients), broad-spectrum antibiotics (5 patients), and antineoplastic agents (4 patients); 14 patients had no identifiable risk. Death was the usual outcome, despite treatment of patients with amphotericin B. In cases of AIDS and invasive aspergillosis, early diagnosis may lead to improved outcome.