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Biomedical subjects

Daniel J Sheehan

Publications and source records attributed to Daniel J Sheehan.

14 recordsLinked to original sources

Bactericidal activity and resistance development profiling of dalbavancin.

Dalbavancin, a semisynthetic lipoglycopeptide being developed for the treatment of skin and skin structure infections (SSSIs), has a half-life of 5 to 7 days in humans and offers promise for a convenient weekly dosing regimen. We studied the in vitro bactericidal activity of dalbavancin against target organisms, using the concentrations that are maintained in human blood with the proposed dosage regimen. Dalbavancin minimal bactericidal concentrations (MBCs) were or=3-log10 decrease in their viable counts when they were exposed to>or=1 microg/ml of dalbavancin for 24 h. Resistance development studies by both direct selection (resistance frequency, <10(-10)) and serial passage failed to produce stable mutants with decreased susceptibility to dalbavancin. These observations suggest that dalbavancin will be an effective choice for the management of patients with SSSIs.

Anti-Bacterial Agents↗

Activity of linezolid against 3,251 strains of uncommonly isolated gram-positive organisms: report from the SENTRY Antimicrobial Surveillance Program.

Linezolid was tested against 32 species of uncommonly isolated gram-positive organisms (3,251 strains) by reference MIC methods and found to be highly active (MIC50 range, 0.25 to 2 microg/ml; MIC90 range, 0.25 to 2 microg/ml). Only one isolate (viridans group streptococcus; 0.03% of tested strains) was resistant to linezolid.

Acetamides↗

Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States.

BACKGROUND: The virulence, antimicrobial resistance, and prevalence of S. aureus underscores the need for up-to-date and extensive insights regarding antimicrobial susceptibility trends. One approach to meet this need is analysis of clinical laboratory-based surveillance data. METHODS: Data from The Surveillance Network-USA (TSN), an electronic surveillance network that collects microbiology data from 300 clinical microbiology laboratories across the United States, were used as the source for analysis that included prevalence of S. aureus in clinical specimens, MRSA and multi-drug resistance phenotype rates and trends according to patient location, geographic distributions, and specimen source. RESULTS: S. aureus was the most prevalent species isolated from inpatient specimens (18.7% of all bacterial isolates) and the second most prevalent (14.7%) from outpatient specimens. In March 2005 MRSA rates were 59.2%, 55%, and 47.9% for strains from non-ICU inpatients, ICU, and outpatients, respectively. This trend was noted in all nine US Bureau of Census regions and multi-drug resistance phenotypes (resistance to > or = 3 non-beta-lactams) was common among both inpatient MRSA (59.9%) and outpatient MRSA (40.8%). Greater than 90% of multi-drug resistant MRSA were susceptible to trimethoprim-sulfamethoxazole, linezolid, and vancomycin. CONCLUSION: Prevalence of MRSA among both inpatient and outpatient specimens continues to increase with multi-drug resistance as a common phenotype. Continued emergence of outpatient MRSA that exhibit multi-drug resistant phenotypes has important implications for developing and evolving outpatient treatment guidelines.

Drug Resistance, Multiple, Bacterial↗

Application of fluorescent probes to study structural changes in Aspergillus fumigatus exposed to amphotericin B, itraconazole, and voriconazole.

The broad objective of this study was to document patterns of structural changes following antifungal treatment, and to determine any relationship with minimum inhibitory concentration (MIC) of an antifungal. Three clinical isolates of Aspergillus fumigatus, with high, intermediate, and low amphotericin B (AB), itraconazole (IZ), and voriconazole (VZ) MICs were studied in 24-well plates with cover slips. The fluorescent probes used were Calcofluor White (cell wall), propidium iodide (nucleus), and MitoTracker Green FM (mitochondria). Fluorescent microscopy as early as 3-h after exposure revealed that AB treated hyphae had intact cell wall with deformed mitochondria and nuclei while IZ and VZ treated hyphae revealed no intact cell wall, and deformation of mitochondria and nuclei. At 48 h, AB treated cells revealed rupture of hyphae and disintegration of mitochondria, and nuclei, IZ treated hyphae were swollen with disintegration of mitochondria, and nuclei while VZ treated hyphae showed rupture and disintegration of mitochondria and nuclei. The structural changes for the three strains studied were similar in fluorescent microscopy as long as the incubation time and their respective MICs were used. Thus, AB, IZ, and VZ induced gross organelle defects in A. fumigatus nuclei, mitochondria, and cell wall, which were consistent with respective MICs of antifungals used.

Amphotericin B↗

Selection of a surrogate agent (vancomycin or teicoplanin) for initial susceptibility testing of dalbavancin: results from an international antimicrobial surveillance program.

The immediate lack of market-dominating commercial products (Vitek or MicroScan) for susceptibility testing of the new glycolipopeptide, dalbavancin, requires a surrogate marker agent to assist microbiologists in the correct categorization of potentially indicated species (staphylococci and streptococci). Error-rate analyses for 16,749 isolates using vancomycin or teicoplanin results to categorize dalbavancin susceptibilities demonstrated that both glycopeptide agents were highly predictive of dalbavancin-susceptible results (nearly 100%) with only a rare minor error. Vancomycin test results most reliably predict dalbavancin susceptibility until validated commercial reagents become available for direct testing in clinical practice.

Anti-Bacterial Agents↗

Cutaneous draining sinus tract of odontogenic origin: unusual presentation of a challenging diagnosis.

A 44-year-old woman presented with a chronically draining lesion on her cheek just lateral to the nasofacial sulcus. The lesion was refractory to treatment with oral antibiotics. Physical examination revealed poor dentition, and a panoramic radiograph demonstrated periapical abscesses in the maxillary right lateral incisor and canine. A diagnosis of cutaneous fistula of odontogenic origin was made, and the patient was treated with tooth extraction. The cutaneous fistula subsequently resolved. Intraoral examinations and radiographs are critical for making the diagnosis of cutaneous draining sinus tract of odontogenic origin. Many patients undergo unnecessary surgical therapies before having the correct diagnosis made, but root canal therapy or surgical extraction is the treatment of choice. A dental origin must be considered for any chronically draining sinus of the face or neck.

Adult↗

The effect of sunless tanning on behavior in the sun: a pilot study.

BACKGROUND: In the United States, indoor tanning is a booming industry and contributes to the ultraviolet light (UVL) burden that ultimately leads to skin cancer. "Sunless" tanning methods that avoid UVL exposure may represent a safe alternative. However, the effects of sunless tanning methods on ultraviolet light-related behaviors have never been investigated. METHODS: Anonymous survey of 121 individuals who underwent a spray-on sunless tanning treatment between February and May 2004. RESULTS: Women completed 107 surveys. Men completed 14 surveys. The majority of individuals reported that they had not or would not change their time spent outdoors or their sunscreen use as a result of undergoing sunless tanning. However, 73% of individuals who had used UVL tanning beds said they had decreased or would decrease their UVL tanning bed use. CONCLUSION: Sunless tanning is associated with a self-reported decrease in traditional UVL tanning bed use among tanning bed users. Physicians should advocate the use of sunless tanning to their patients who use traditional UVL tanning beds as a means of decreasing their UVL exposure and cancer risk.

Adolescent↗

In vitro activity of linezolid against key gram-positive organisms isolated in the united states: results of the LEADER 2004 surveillance program.

Since the approval of linezolid in 2000, sporadic reports of resistance have been given and a greater understanding of the underlying mechanisms of resistance has been gained. However, since these developments, an updated status of the in vitro activity of linezolid against gram-positive organisms from the United States has not been reported. The LEADER 2004 surveillance initiative was undertaken to obtain current and representative data on the activity of linezolid against key species, including isolates with significant resistance phenotypes. Organisms were isolated during 2004 and included 2,872 Staphylococcus aureus, 496 coagulase-negative staphylococcus (CNS), 428 Enterococcus faecalis, 196 Enterococcus faecium, and 422 Streptococcus pneumoniae isolates. All S. aureus isolates (54.2% oxacillin resistant) were susceptible to linezolid (MIC90 = 2 microg/ml); MIC distributions were consistent, regardless of oxacillin or multidrug resistance status. For CNS, one nonsusceptible isolate was encountered (Staphylococcus epidermidis; MIC = 32 microg/ml), but overall, the MIC(90) (1 microg/ml) was lower than that obtained with S. aureus. For E. faecalis and E. faecium, 99.5% and 96.4% of isolates, respectively, were linezolid susceptible. Both species had an MIC90 of 2 microg/ml, and MIC distributions did not vary with the vancomycin susceptibility status of the populations analyzed. Linezolid nonsusceptibility was not encountered among the S. pneumoniae isolates. These findings indicate that linezolid nonsusceptibility has remained rare among staphylococci and uncommon and sporadic among enterococci. Nonetheless, careful and ongoing monitoring of the in vitro effectiveness of linezolid will be needed so that any changes to the current status may be detected as soon as possible.

Acetamides↗

Combination treatment of invasive fungal infections.

The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections.

Animals↗

Pyogenic granuloma arising within a port-wine stain.

Pyogenic granulomas are common overgrowths of vascular tissue that usually arise on the face, lips, or hands after episodes of minor trauma or during pregnancy. Pyogenic granulomas rarely have been reported to arise in congenital capillary malformations such as port-wine stains, a presentation that most often occurs after laser treatment of port-wine stains or in the setting of pregnancy. This co-occurrence of the 2 lesions represents an underreported event, and the presentation can be alarming or mimic malignancy when there is no prior history of trauma or other known circumstances in which pyogenic granulomas occur. We report a case of a pyogenic granuloma emerging within a port-wine stain in a 35-year-old man with no predisposing factors. A review of the literature regarding pyogenic granulomas that arise within port-wine stains is presented and yields informative conclusions regarding the clinical scenarios where this sometimes alarming event is likely to happen.

Adult↗

Deep venous thrombosis after high-dose intravenous immunoglobulin in the treatment of pemphigus vulgaris.

A 43-year-old black man with pemphigus vulgaris was started on intravenous immunoglobulin (IVIg) therapy after his disease was found to be refractorry to prednisone alone and prednisone in combination with mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, and oral cyclophosphamide. The patient subsequently developed a deep venous thrombosis (DVT) that was attributed to the IVIg. IVIg has been associated with numerous thrombotic complications such as pulmonary embolism and myocardial infarction. Traditional risk factors for thrombotic complications, such as hypertension, a history of coronary artery disease, and immobility, should be considered as relative contraindications to IVIg therapy.

Adult↗

Atrophic dermatofibrosarcoma protuberans: a case report and reappraisal of the literature.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous malignancy. Unusual presentations described as atrophic have been documented. A case of DFSP with both clinical and histologic atrophy is presented, and all cases purporting atrophy with this tumor are reviewed. Meaningful trends are extracted from this data. In addition, the imprecise use of the term atrophic in regard to DFSP is clarified. We maintain that the variant of atrophic DFSP that mimics atrophoderma or anetoderma, as in this case, is the rarest variant of atrophic DFSP. Atrophic DFSP should be in the differential for depressed lesions on the trunks of women or on the lower extremities of children.

Adult↗

Video game induced knuckle pad.

Controversy and concern surround the video game playing fascination of children. Scientific reports have explored the negative effects of video games on youth, with a growing number recognizing the actual physical implications of this activity. We offer another reason to discourage children's focus on video games: knuckle pads. A 13-year-old black boy presented with an asymptomatic, slightly hyperpigmented plaque over his right second distal interphalangeal joint. A punch biopsy specimen confirmed knuckle pad as the diagnosis, and a traumatic etiology from video game playing was suspected. Knuckle pads can be painful, cosmetically unappealing, and refractory to treatment. They can now be recognized as yet another potential adverse consequence of chronic video game playing.

Adolescent↗