Intermediate cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis successfully treated with fluconazole.

American cutaneous leishmaniasis is an endemic anthropozoonosis that exhibits a broad spectrum of clinical presentations. Intermediate/borderline disseminated cutaneous leishmaniasis is a distinct clinical condition that comprises cutaneous disease of a chronic nature, usually occurring as multiple lesions with or without mucosal involvement. The disease is usually caused by parasites of the subgenus Viannia, frequently occurs in context of an underlying disease, and is often resistant to standard antileishmanial therapy. We report a case that was refractory to standard therapy and other second-line drugs, but resolved after treatment with fluconazole, and review the use of fluconazole as a second-line drug in children.

Lymphoepithelioma-like gastric carcinoma: an unusual consequence of Epstein-Barr virus infection in an HIV-infected woman.

Lymphoepithelioma-like-gastric carcinoma (LEL-GC) is an Epstein-Barr virus (EBV)-associated neoplasm of the stomach reported to have a better prognosis than conventional gastric adenocarcinoma. Unlike other EBV-associated malignancies, particularly lymphoproliferative disorders and undifferentiated nasopharyngeal carcinoma, for which risk has been shown to increase in human immunodeficiency virus (HIV) infection, LEL-GC remains rare; only one HIV-infected patient with LEL-GC has been reported previously. We describe an aggressive case of EBV-associated LEL-GC in a woman co-infected with HIV 1 and hepatitis C virus. In situ hybridization of an endoscopic biopsy specimen for EBV-encoded small RNA confirmed the presence of this agent exclusively in the gastric cancer cells. Our patient had recently started antiretroviral therapy, suggesting that immune reconstitution may have been a factor in presentation of this tumour.

Clinical characteristics of bacteraemia caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae in the era of CTX-M-type and KPC-type ß-lactamases.

Clin Microbiol Infect 2012; 18: 887-893 ABSTRACT: A multicentre, case-control study was conducted to assess risk factors and patient outcomes of bacteraemia caused by Enterobacteriaceae producing extended-spectrum ß-lactamases (ESBLs) and Klebsiella pneumoniae carbapenemases (KPCs). One hundred and five and 20 patients with bacteraemia caused by ESBL-producing and KPC-producing organisms were matched to controls who had bacteraemia caused by non-ESBL/KPC-producing organisms, respectively. Independent risk factors for ESBL production included admission from a nursing home (OR 4.64; 95% CI 2.64-8.16), chronic renal failure (OR 2.09; 95% CI 1.11-3.92), the presence of a gastrostomy tube (OR 3.36; 95% CI 1.38-8.18), length of hospital stay before infection (OR 1.02; 95% CI 1.01-1.03), transplant receipt (OR 2.48; 95% CI 1.24-4.95), and receipt of antibiotics with Gram-negative activity in the preceding 30 days (OR 1.76; 95% CI 1.00-3.08). Twenty-eight-day crude mortality rates for patients infected with ESBL-producing or KPC-producing organisms and controls were 29.1% (34/117) and 19.5% (53/272), respectively (OR 1.70; 95% CI 1.04-2.80). On multivariate analysis, inadequate empirical therapy (OR 2.26; 95% CI 1.18-4.34), onset of bacteraemia while in the intensive-care unit (OR 2.74; 95% CI 1.47-5.11), Apache II score (OR 1.17; 95% CI 1.12-1.23) and malignancy (OR 2.66; 95% CI 1.31-5.41) were independent risk factors for mortality. CTX-M was the most common ESBL type in Escherichia coli, whereas SHV predominated in Klebsiella spp. and Enterobacter spp.

Successful treatment of Old World cutaneous leishmaniasis caused by Leishmania infantum with posaconazole.

Old World cutaneous leishmaniasis is a widespread and potentially disfiguring protozoal infection that is endemic in the Mediterranean basin, Africa, and parts of Asia. Human infection is caused by several species of Leishmania parasites, such as Leishmania infantum. Available systemic and topical treatments vary in efficacy and are often unjustified due to their toxicity. We report on a case that was treated with posaconazole, a drug typically considered an antifungal agent but which also targets specific metabolic pathways of the parasite.

Use and efficacy of tuberculosis infection control practices at hospitals with previous outbreaks of multidrug-resistant tuberculosis.

OBJECTIVE: To evaluate the implementation and efficacy of selected Centers for Disease Control and Prevention guidelines for preventing spread of Mycobacterium tuberculosis. DESIGN: Analysis of prospective observational data. SETTING: Two medical centers where outbreaks of multidrug-resistant tuberculosis (TB) had occurred. PARTICIPANTS: All hospital inpatients who had active TB or who were placed in TB isolation and healthcare workers who were assigned to selected wards on which TB patients were treated. METHODS: During 1995 to 1997, study personnel prospectively recorded information on patients who had TB or were in TB isolation, performed observations of TB isolation rooms, and recorded tuberculin skin-test results of healthcare workers. Genetic typing of M tuberculosis isolates was performed by restriction fragment-length polymorphism analysis. RESULTS: We found that only 8.6% of patients placed in TB isolation proved to have TB; yet, 19% of patients with pulmonary TB were not isolated on the first day of hospital admission. Specimens were ordered for acid-fast bacillus smear and results received promptly, and most TB isolation rooms were under negative pressure. Among persons entering TB isolation rooms, 44.2% to 97.1% used an appropriate (particulate, high-efficiency particulate air or N95) respirator, depending on the hospital and year; others entering the rooms used a surgical mask or nothing. We did not find evidence of transmission of TB among healthcare workers (based on tuberculin skin-test results) or patients (based on epidemiological investigation and genetic typing). CONCLUSIONS: We found problems in implementation of some TB infection control measures, but no evidence of healthcare-associated transmission, possibly in part because of limitations in the number of patients and workers studied. Similar evaluations should be performed at hospitals treating TB patients to find inadequacies and guide improvements in infection control.

Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression.

Bone destruction, caused by aberrant production and activation of osteoclasts, is a prominent feature of multiple myeloma. We demonstrate that myeloma stimulates osteoclastogenesis by triggering a coordinated increase in the tumor necrosis factor-related activation-induced cytokine (TRANCE) and decrease in its decoy receptor, osteoprotegerin (OPG). Immunohistochemistry and in situ hybridization studies of bone marrow specimens indicate that in vivo, deregulation of the TRANCE-OPG cytokine axis occurs in myeloma, but not in the limited plasma cell disorder monoclonal gammopathy of unknown significance or in nonmyeloma hematologic malignancies. In coculture, myeloma cell lines stimulate expression of TRANCE and inhibit expression of OPG by stromal cells. Osteoclastogenesis, the functional consequence of increased TRANCE expression, is counteracted by addition of a recombinant TRANCE inhibitor, RANK-Fc, to marrow/myeloma cocultures. Myeloma-stroma interaction also has been postulated to support progression of the malignant clone. In the SCID-hu murine model of human myeloma, administration of RANK-Fc both prevents myeloma-induced bone destruction and interferes with myeloma progression. Our data identify TRANCE and OPG as key cytokines whose deregulation promotes bone destruction and supports myeloma growth.

Increased gastric epithelial cell apoptosis associated with colonization with cagA + Helicobacter pylori strains.

Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated "blindly" using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization.

Helicobacter pylori decreases gastric mucosal glutathione.

Activation of oxidative stress pathways may contribute to gastric epithelial damage and mutagenesis caused by Helicobacter pylori. We measured the effect of H. pylori on the concentrations of reduced glutathione (GSH), an important endogenous defense against oxidant damage, in gastric epithelial cells in vivo and in vitro. GSH concentrations were significantly lower in gastric biopsies from 19 H. pylori-infected patients than 38 normal controls, and correlated inversely with inflammatory cell numbers. In vitro, H. pylori initially increased GSH levels in AGS cells, but subsequently depleted intracellular GSH stores completely after 24 h. No GSH was detected in H. pylori. Our data suggest that diminished GSH levels with H. pylori colonization of the gastric mucosa may be due to a direct effect of the bacterium as well as through the associated inflammatory response.

Chronic Helicobacter pylori infection induces an apoptosis-resistant phenotype associated with decreased expression of p27(kip1).

Helicobacter pylori infection is associated with the development of gastric cancer. In short-term coculture with AGS gastric cells, H. pylori inhibits cell cycle progression and induces dose-dependent apoptosis. Based on the concept that an imbalance between proliferation and apoptosis may contribute to the emergence of gastric cancer, we chronically exposed AGS cells to H. pylori as a model of chronic exposure in humans. The AGS derivatives selected by this process were stably resistant not only to H. pylori-induced apoptosis but also to apoptosis induced by other enteric bacteria and by several toxic agents including radiation and cancer chemotherapy. Like the parental AGS cells, the derivatives underwent G(1)/S-phase cell cycle inhibition in response to H. pylori. The AGS derivatives displayed a marked decrease in cellular levels of the cell cycle control protein p27(kip1). We found a similar decrease in epithelial cell p27(kip1) expression in gastric biopsy specimens from H. pylori-infected patients. These findings are consistent with observations that link decreases in the p27(kip1) level to increased susceptibility to cancer in mice with p27(kip1) deleted and to a poor prognosis of gastric cancer in humans. This is the first demonstration that bacterial infection can lead to apoptosis resistance and to cross-resistance to other inducers of apoptosis such as bacteria, chemotherapeutic agents, and radiation. The development of apoptosis resistance and downmodulation of p27(kip1) may contribute to the increased risk for gastric cancer observed in humans chronically exposed to H. pylori.

Helicobacter pylori inhibits the G1 to S transition in AGS gastric epithelial cells.

Infection with the bacterium Helicobacter pylori is associated epidemiologically with development of gastric cancer. To better understand the role of H. pylori in carcinogenesis, we examined the effects of H. pylori on cell cycle-related events in the AGS gastric cancer cell line. During coculture, wild-type, toxigenic, cagA-positive H. pylori induced both apoptosis and inhibition of cell cycle progression at G1-S in AGS cells. These effects were most apparent in AGS cells synchronized by serum-deprivation and then stimulated to progress through the cell cycle by refeeding. An isogenic cagA-negative mutant H. pylori, produced similar effects. In contrast to changes induced by 5-fluorouracil, the inhibition of cell cycle progression from G1 to S caused by H. pylori was not accompanied by sustained changes in p53 or p21cip1, but was associated with reduced expression of p27kip1 and inhibition of transcriptional activation of the serum-response element of c-fos. Our results indicate that H. pylori inhibits cell cycle progression at G1-S and induces apoptosis, associated with reduced expression of p27kip1 in AGS gastric cancer cells. In vivo, similar effects as a result of H. pylori infection may lead to potentially deleterious compensatory hyperproliferation by nonneoplastic gastric epithelial cells.

Povidone iodine and skin disinfection before initiation of epidural anesthesia.

BACKGROUND: Povidone iodine (PI) solution is used commonly for skin disinfection before epidural and spinal anesthesia. Although there have been reports indicating the presence of microbial contaminants in PI solution, none have evaluated the prevalence of PI contamination. The aims of this study were to assess the frequency of bacterial contamination of previously opened bottles of PI solution and to compare the effectiveness of new and previously opened bottles of PI solution for skin disinfection. METHODS: Twenty previously opened and ten previously unopened multiple-use bottles of PI solution were evaluated for microbial contamination. In addition, final swabs and PI solution used for skin disinfection in 80 patients undergoing elective epidural analgesia were evaluated. RESULTS: The inside of the bottle cap or the PI solution from 40% of the multiple-use PI bottles in use were contaminated. There was no growth from any previously unused PI bottles. Povidone iodine from newly opened bottles provided more effective skin decontamination than did solution from previously opened bottles. CONCLUSIONS: Multiple-use PI bottles in normal use may become contaminated by bacteria. In addition, PI solution from previously opened bottles was less effective than PI from previously unopened bottles. Based on these findings, if PI solution is chosen for skin antisepsis before initiation of epidural and spinal anesthesia, only single-use containers should be used.

Apoptosis in gastric epithelial cells is induced by Helicobacter pylori and accompanied by increased expression of BAK.

Carriage of the bacterium H. pylori in the human stomach is associated with evidence of increased epithelial cell apoptosis. This may be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. The ability of H. pylori to directly induce epithelial apoptosis was examined in vitro by fluorescence and electron microscopy, flow cytometry, and DNA fragmentation ELISA. The induction of apoptosis by H. pylori was time and concentration-dependent and inhibited by preventing direct bacterial-epithelial cell contact. Apoptosis was accompanied by increased expression of Bak, with little change in expression of other Bcl-2 family proteins. The expression of Bak was also increased in gastric biopsies from patients colonized by H. pylori. Thus, H. pylori induces gastric epithelial cell apoptosis, by a Bak-dependent pathway.

Chronic bacterial enteropathy in patients with AIDS.

Enteric infection with adherent bacteria has been seen in a person with chronic diarrhea who was infected with the human immunodeficiency virus. In this study, adherent bacteria were seen in 17% of all patients with AIDS evaluated during a 1-year period. The infection was centered in the cecum and right colon. Three distinct histopathologic patterns of adherence were observed: attaching and effacing lesions, bacteria intercalated between microvilli, and aggregates of bacteria more loosely attached to the damaged epithelium. The infections were associated with weight loss (P < .005) and peripheral blood CD4+ cell of counts < 100/mm3 (P < .05). Eight of 9 patients treated with antibiotics had symptomatic improvement. Bacterial cultures of rectal biopsies frozen at endoscopy yielded Escherichia coli in 12 of 18 cases; aggregative adherence was seen in 6. Isolates from 2 cases hybridized with a DNA probe encoding aggregative properties. These results suggest that chronic infection with adherent bacteria may produce a syndrome of AIDS-associated diarrhea and wasting.