Multiple-species candidemia in patients with cancer

BACKGROUND: Candidemia is a common cause of bloodstream infections in patients with cancer, with the majority of these infections being caused by a single Candida species. Studies of multiple-species candidemia (MSC) have rarely been reported. METHODS: The authors identified 33 patients with cancer who had candidemia (diagnosed between 1993 and 2000) caused by more than 1 Candida species. This group of 33 patients was compared with a control group of 66 patients with cancer who had C. albicans candidemia that arose soon before or soon after each case of MSC that was investigated in the current study. RESULTS: Patients with MSC, compared with control patients, were more likely to have leukemia (33% vs. 8%; P = 0.001), to have had prolonged neutropenia before the onset of their infection (mean +/- standard deviation, 10 +/- 17 days vs. 3 +/- 6 days; P = 0.02), and to have received chemotherapy within 1 month before their infection (42% vs. 18%; P = 0.01). Patients with MSC also had higher Acute Physiology and Chronic Health Evaluation II scores at the onset of infection (score > or = 16, 45% vs. 26%; P = 0.05) and were more likely to have received previous antifungal prophylaxis compared with patients who had candidemia caused by C. albicans (33% vs. 11%; P = 0.006). The response of C. albicans candidemia to single-agent antifungal therapy was significantly better than that of MSC (69% vs. 35% P = 0.004). CONCLUSIONS: In patients with cancer, MSC was more likely to occur as breakthrough candidemia, predominantly in those with leukemia and prolonged neutropenia, and was associated with suboptimal responses to single-agent antifungal therapy.     

Elevation of the Ulcer Base in Cases Treated with an H2-Blocker —Difference between an Elevated Type of Gastric Ulcer Scar and a White Elevated Lesion—

Abstract: A white elevated lesion (WEL) was noted in 7 out of 227 ulcer patients treated with an H₂-blocker. These were compared with eight patients with an elevated type of gastric ulcer scars The elevated type of gastric ulcer scar (ES) is an elevated lesion covered with regenerating epithelium, showing no whitish exudate, and is foveolar hyperplasia in the histological picture of biopsy. The period prior to the formation of an elevated lesion was as short as 4 weeks on average, and the formed elevated lesion retained the elevated from for as long as several months to several years. The WEL is an elevated lesion covered with whitish exudate, and shows granulation in the histological picture of biopsy. The period prior to the formation of an elevated lesion was as short as 3 weeks on average, and the formed elevated lesion became flattened in a relatively short period of several weeks to several months. From the above results the ES and the WEL are different in the clinical course, morphology and the histological picture, and considered to be of a different quality.     

Heme from Alzheimer's brain inhibits muscarinic receptor binding via thiyl radical generation

An endogenous inhibitor (<3500 Da) of antagonist binding to the muscarinic acetylcholine receptor (mAChR) has been reported to be elevated 3-fold in Alzheimer's disease (AD) brain. This endogenous inhibitor was found to require the presence of reducing agents such as reduced glutathione (GSH) for optimal activity. In the presence of GSH, the inhibitor was shown to generate thiyl radicals which irreversibly inhibited the mAChR. We now report that the inhibitor contains free heme, a well-established source of oxidative stress capable of generating free radicals and causing neurotoxicity. While FeSO₄, microperoxidase and hemin all inhibited antagonist binding to the mAChR, only hemin shared the inhibitor's requirement for GSH. Both the free radical scavengers Trolox and Mn²⁺, and the metal chelator, EDTA, blocked the activity of the endogenous AD inhibitor and of hemin. Heme oxygenase-1 (HO-1) markedly reduced the activity of both the endogenous AD inhibitor and hemin, indicating that the endogenous inhibitor contains heme. Mass spectrometric analysis confirmed the presence of free heme and heme fragments in fractions of the endogenous AD inhibitor. The antioxidants estrogen, vitamin E and vitamin C all protected the mAChR from irreversible inhibition by the endogenous inhibitor or hemin. These antioxidants may function to protect the integrity of the mAChR in vivo and may have therapeutic potential in AD where free heme could be a source of oxidative stress.     

Spontaneous necrosis of the skin associated with cryofibrinogenemia,cryoglobulinemia, and homocystinuria

Cryofibrinogenemia has been associated with a variety of skin manifestations including purpura, livedo reticularis, and ulceration. Our patient, who had undergone axillobifemoral bypass 5 years previously, presented following the spontaneous development of a necrotic wound involving the left groin scar. The location of the wound suggested the possibility of underlying graft infection, but indium-111 white blood cell scan and MRI failed to show any evidence of infection. The patient was initially treated with oral antibiotics and outpatient debridement with no improvement. A more aggressive approach with inpatient operative debridement and intravenous antibiotics produced moderate improvement. Three months later, the patient developed an identical necrotic wound in the right groin and subsequently a third lesion involving a scar distant from any of the patient's grafts. No evidence of active vasculitis was seen on microscopic examination of the excised tissues. Cryoglobulin and cryofibrinogen assays were positive, and urinary and plasma homocysteine levels were elevated. The patient was subsequently treated with stanozolol, a low-methionine diet, and outpatient intravenous antibiotics with rapid improvement of her wounds. In patients with spontaneous ulceration of the extremities, particularly when they do not respond appropriately to standard therapy, the possibility of cryoglobulinemia or cryofibrinogenemia should be considered.Presented at the Fourteenth Annual Meeting of the Southern California Vascular Surgical Society, September 15–17, 1995, La Jolla, Calif.     

Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients

The purpose of this prospective randomized study was to compare the efficacy and safety of imipenem and cefoperazone-sulbactam combined with vancomycin for the treatment of fever in neutropenic cancer patients. Patients were assigned to either imipenem 500 mg/m² (500 mg for bone marrow transplant recipients) every 6 h or cefoperazone (2 g)-sulbactam (1 g) every 8 h. All patients received vancomycin 1 g every 12 h. A total of 457 febrile or infectious episodes occurring in 407 patients were entered in the study. The response rate was 73% for imipenem plus vancomycin and 74% for cefoperazone-sulbactam plus vancomycin among the 369 episodes that could be evaluated. Response rates were comparable for the two regimens with regard to infecting organism, administration of antimicrobial prophylaxis, and neutrophil count and trend. The frequency of side-effects was significantly higher for imipenem plus vancomycin (11 % vs. 5%, p = 0.02), due to therapy-associated nausea and vomiting (5.3% vs. 0%, p = 0.0004). The overall frequency of superinfections was similar with both regimens, butClostridium difficile colitis occurred significantly more often in patients receiving imipenem plus vancomycin (5 vs. 0, p = 0.02). In this study cefoperazone-sulbactam plus vancomycin was an effective alternative to imipenem plus vancomycin for initial therapy of fever in neutropenic patients.     

Ampicillin-sulbactam vs clindamycin in head and neck oncologic surgery. The need for gram-negative coverage.

This study was undertaken to assess whether gram-negative antimicrobial coverage is required in patients undergoing head and neck oncologic surgery. Ampicillin sodium-sulbactam sodium and clindamycin phosphate were compared in a prospective, randomized, parallel, double-blind trial of 212 patients undergoing head and neck procedures involving clean-contaminated wounds. Both antibiotics were given up to 1 hour before surgery and continued at 6-hour intervals after surgery for an additional eight doses. Fourteen infections occurred in the ampicillin-sulbactam-treated group (13.3%) and 29 infections in the clindamycin-treated group (27.1%). From patients receiving clindamycin, 29 gram-negative organisms were isolated, compared with six from those patients receiving ampicillin-sulbactam. This finding supports the need for gram-negative coverage in patients undergoing clean-contaminated head and neck oncologic surgery.