Search PubMed⌕ Search

Biomedical subjects

A Safdar

Publications and source records attributed to A Safdar.

36 records · Page 2Linked to original sources

Curvularia--favorable response to oral itraconazole therapy in two patients with locally invasive phaeohyphomycosis.

Curvularia species are ubiquitous and occasionally lead to infections in humans. In immunosuppressed patients, infections are often serious, and systemic dissemination is not uncommon. The optimal antifungal therapy is unclear. I here present two cases, a healthy man with locally invasive, mulicentric paranasal fungal sinusitis, and a case of progressive verrucal distal onychomycosis that developed while the patient was undergoing accelerated chemotherapy for non-Hodgkin's lymphoma. Both patients showed excellent responses to treatment with itraconazole suspension. Oral itraconazole may provide a safe and effective alternative for patients with locally invasive non-disseminated mycoses due to Curvularia species.

Administration, Oral↗

Seasonal variation in bacterial pathogens isolated from stool samples in Karachi, Pakistan.

OBJECTIVE: To determine the seasonal variation of the commonly isolated bacterial pathogens in stool samples. MATERIAL AND METHODS: A retrospective descriptive study was undertaken of all the stool samples submitted from within Karachi to the Aga Khan University Hospital Laboratory over a period of five years (January 1997- December 2001) in order to determine the commonly isolated bacterial pathogens and to predict their seasonal variation. RESULTS: A total of 16379 stool samples were included in this review. Bacterial isolates were found in 6670 stool samples (culture detection rate=40.7%). The mean age at the time of culture of each sub-group was < or = 1 year group (6.58 +/- 3.1 months), 1-5 years (2.13 +/- 0.94 years), 5-14 years (8.3 +/- 2.6 yrs) and adults (43.2 +/- 18.5 years). Male: Female ratio was 1.2:1. Vibrio cholera 01 Ogawa (32.8%), Campylobacter jejuni (17.3%), Enteropathogenic Escherichia coli (9.9%), Salmonella paratyphi b (6.6%) and Shigella flexneri (6.2%) were the most common organisms isolated. These organisms show a distinct seasonal variation with summer predilection. CONCLUSION: In contrast to the previous studies from South Asia, which have identified E. coil, followed by Vibrio cholerae as the most common enteric isolates, we found Vibrio cholera 01 Ogawa followed by Campylobacter jejuni as the most common enteric pathogens isolated in an urban setting. It is important to consider seasonal variation when empirically treating diarrheal diseases in our region.

Adolescent↗

Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation. Scedosporiasis and recent advances in antifungal therapy.

Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation. We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease. This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis. Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue. A broad-spectrum triazole-based agent (voriconazole/UK-109, 496--Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991--Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk.

Adult↗

Listeriosis in recipients of allogeneic blood and marrow transplantation: thirteen year review of disease characteristics, treatment outcomes and a new association with human cytomegalovirus infection.

Listeriosis is uncommon in recipients of allogeneic blood, marrow and organ transplantation. Six patients with systemic Listeria monocytogenes infection during 1985-1997 at Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center are described. In two male and four female patients, the median duration from transplantation to isolation of L. monocytogenes was 62.5 (range 29 to 821) days. Among five allogeneic marrow transplant recipients, four (80%) received HLA antigen matched, T cell-depleted grafts from three unrelated and a single related donor. One patient underwent mismatched-related marrow graft transplant. Cord stem cell transplantation was performed in a single patient. Two required therapy for graft-versus-host disease (GVHD). The 13 year incidence of systemic Listeria infections was 0.47 percent. All six presented with fever (>39 degrees C), and L. monocytogenes bloodstream invasion. Mental status changes and meningioencephalitis were observed in two (33.3%). A concurrent primary opportunistic infection was present in five individuals (83.3%), and four (80%) were being treated for acute human cytomegalovirus (HCMV) viremia. Sixty-six percent responded to therapy and two died from unrelated, non-listeric causes. Systemic listeriosis was uncommon in our high-risk allogeneic blood and marrow transplantation population, and response to therapy with parenteral ampicillin and gentamicin was excellent. The association between primary HCMV reactivation and subsequent listeric infection emphasizes the significance of HCMV-related dysfunction in hosts' cellular immune responses, especially in the setting of allogeneic transplantation.

Adolescent↗

Prospective evaluation of Candida species colonization in hospitalized cancer patients: impact on short-term survival in recipients of marrow transplantation and patients with hematological malignancies.

Most hematogenous candidiasis originates from endogenous host flora. The impact of clinically prominent Candida colonization on short-term mortality ( 50 colonies of Candida from non-sterile sites. Fourteen (7.1%) patients were granulocytopenic (ANC <or=100/microl). Nineteen (9.8%) had undergone marrow transplantation, 26 (13.5%) had a hematologic malignancy and 129 (66.5) had non-hematologic cancer. Candida isolates (216) were collected form 210 specimens. Fifty-three (27.5%) patients died; 25 (19.4%) with solid tumors, compared to 16 (61.5%) with hematological malignancy, and 11 (57.9%) BMT recipients (P < 0.001). No deaths were seen in patients with AIDS, and one (7.7%) in a patient with a benign condition (P < 0.001). Twenty-six (29.2%) patients with respiratory tract, 13 (23.2%) with gastrointestinal tract, and three (14.3%) with genitourinary tract colonization died. In patients with multiple-site colonization, mortality was significantly higher (45.5%) (P < 0.05). Mortality was higher in patients with C. glabrata (52.9%) and C. krusei (75%) colonization than with C. albicans (24.1%) (P < 0.025). This study shows that patients with hematologic cancer and recipients of marrow transplant with Candida colonization of multiple body sites, and colonization with C. glabata or C. krusei have poor survival.

AIDS-Related Opportunistic Infections↗

Infectious morbidity in critically ill patients with cancer.

Infection frequently complicates the course of cancer treatment and often adversely affects the outcome. Patients have a greater tendency for acquiring infections caused by opportunistic microorganisms. Agents with low virulence potential may lead to invasive and often life-threatening infections because of altered host immune function. The immune dysfunction may be caused by the underlying malignancy, by antineoplastic chemotherapy, or by invasive procedures during supportive care.

Agranulocytosis↗

Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome.

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.

Adolescent↗

Prospective study of Candida species in patients at a comprehensive cancer center.

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of Candida spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349 Candida isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS. Candida albicans was the predominant species (67.3%); among 114 non-albicans Candida spp., C. glabrata (45.6%) was the most frequent, followed by C. tropicalis (18.4%), C. parapsilosis (16.6%), and C. krusei (9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of C. albicans strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of C. glabrata strains were resistant to fluconazole (MIC > or = 64 microg/ml) and itraconazole (MIC > or = 1 microg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant C. albicans (P = 0.005, OR 36), although this relationship was not seen in C. glabrata isolates (P = 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.

Antifungal Agents↗

The myogenic component in distention-induced peristalsis in the guinea pig small intestine.

In an in vitro model for distention-induced peristalsis in the guinea pig small intestine, the electrical activity, intraluminal pressure, and outflow of contents were studied simultaneously to search for evidence of myogenic control activity. Intraluminal distention induced periods of nifedipine-sensitive slow wave activity with superimposed action potentials, alternating with periods of quiescence. Slow waves and associated high intraluminal pressure transients propagated aborally, causing outflow of content. In the proximal small intestine, a frequency gradient of distention-induced slow waves was observed, with a frequency of 19 cycles/min in the first 1 cm and 11 cycles/min 10 cm distally. Intracellular recording revealed that the guinea pig small intestinal musculature, in response to carbachol, generated slow waves with superimposed action potentials, both sensitive to nifedipine. These slow waves also exhibited a frequency gradient. In addition, distention and cholinergic stimulation induced high-frequency membrane potential oscillations (~55 cycles/min) that were not associated with distention-induced peristalsis. Continuous distention produced excitation of the musculature, in part neurally mediated, that resulted in periodic occurrence of bursts of distally propagating nifedipine-sensitive slow waves with superimposed action potentials associated with propagating intraluminal pressure waves that caused pulsatile outflow of content at the slow wave frequency.

Action Potentials↗

Non-myeloablative allogeneic transplantation ('microallograft') for refractory myeloma after two preceding autografts: feasibility and efficacy in a patient with active aspergillosis.

A 59-year-old man with a 4-year history of light chain myeloma relapsing after two preceding autografts and salvage therapy with thalidomide underwent a peripheral blood stem cell (PBSC) transplant from his HLA-identical sister after conditioning with 100 mg/m2 melphalan. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine. Despite pulmonary infiltrates and sinusitis at the time of the allograft, it was decided to proceed with the transplant because the myeloma was refractory and rapidly progressive. Sputum cultures obtained 2 days before the allograft grew Aspergillus fumigatus 2 days post transplant. A fumigatus grew repeatedly on specimens obtained post transplant. Prompt hematologic recovery was seen with full donor-type chimerism. The fungal infection subsided gradually on a combination of amphotericin B lipid complex and itraconazole. A second aliquot of donor PBSC was infused electively on day +42 to induce graft-versus-myeloma. Complete remission of the myeloma was achieved by 75 days post transplant. No acute GVHD was seen. No chronic GVHD was seen at 16 weeks when he received the third PBSC infusion. He is currently alive and well in remission 9 months post transplant. This case demonstrates the safety and potential usefulness of allogeneic PBSC transplantation with reduced-intensity conditioning in patients with markedly compromised performance status.

Antineoplastic Agents, Alkylating↗