A review of clinical failures associated with macrolide-resistant Streptococcus pneumoniae

The emerging reports of clinical failures using macrolides and their associations with macrolide-resistant Streptococcus pneumoniae prompted us to review the literature describing these cases. Thirty-three cases reporting macrolide treatment failure during treatment of pneumococcal infections were available for review. The most prevalent diagnosis (24/27 or 88.8% of available diagnoses) was community-acquired pneumonia (CAP). Previous medical history included cardiopulmonary disease in eight (24.2%) and immunocompromised states in five (15.1%) patients. The majority, 31/33 (93.9%) of patients received oral macrolide treatment in an outpatient setting. S. pneumoniae was isolated from the blood in 26 (78.8%) of 33 patients, three (9.1%) patients had bacteria present in both blood and cerebrospinal fluid, two (6%) patients grew S. pneumoniae from blood and bronchial washings and two (6%) patients had positive sputum cultures. The MLS(B) phenotype was the most predominant phenotype present in 12 (63.2%) of 19 patients. After failing initial macrolide treatment, 26 (78.8%) of 33 patients received parenteral antibiotic treatment. Of 33 patients admitted to hospital, 29 (87.8%) had their outcome described as 'survived'.     

Laser trabecular sclerosis for chronic hypotony after vitreoretinal surgery

PURPOSE: To perform a pilot study of laser trabecular sclerosis (LTS) for chronic ocular hypotony after vitreoretinal surgery. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Three patients with chronic hypotony after vitreoretinal procedures underwent LTS. All patients had undergone complex vitreoretinal surgery with attached retinas postoperatively but with persistent hypotony and poor vision. INTERVENTION: Laser trabecular sclerosis was performed in a fashion similar to laser trabeculoplasty, using a 100-microm spot, 800 to 1000 mW power at 0.1 seconds, and applying heavy confluent treatment in >/=1 sessions throughout the angle where trabecular meshwork was visible. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), best spectacle-corrected visual acuity, and complications were studied. RESULTS: In 1 patient, a single session of LTS was followed by an increase in IOP of approximately 4 mm, with subjective and objective improvement in vision. A second patient exhibited improvement in IOP and visual acuity after 3 sessions of LTS. A third patient underwent 3 sessions of LTS without improvement in IOP or vision. CONCLUSION: Given the limitations of this small series, including the lack of a randomized prospective design, it is not possible to determine the safety or efficacy of LTS, but this study does suggest that this procedure could play a therapeutic role in some patients with chronic symptomatic hypotony after complex intraocular surgery. Further study is warranted.     

Chronic invasive fungal sinusitis: a report of two atypical cases

The purpose of this article is to describe a chronic variant of invasive fungal sinusitis (IFS) and discuss its management. This is a retrospective review of two cases of IFS that were characterized by atypical clinical courses. Patient 1 was a 75-year-old man with noninsulin-dependent diabetes mellitus who came to us with a 5-month history of headache. Computed tomography detected an opacified left sphenoid sinus. After the man failed to respond to medical therapy, he underwent a left endoscopic sphenoidotomy. Pathologic examination revealed that septate, branching fungal hyphae had invaded the soft tissues. The patient was started on oral itraconazole, but later switched to intravenous amphotericin B in response to intracranial extension. The man's disease stabilized, but he died a little more than 1 year later of unrelated causes. Patient 2 was an otherwise healthy 41-year-old woman who came to us with nasal congestion and unilateral nasal polyps. She underwent endoscopic sinus surgery. Pathologic examination identified granulomatous sinusitis and septate, branching fungal hyphae that had invaded the soft tissue of the middle turbinate. The patient was not treated with systemic antifungal medications because of the localized nature of the fungal invasion and the lack of bone invasion or erosion. She has now been symptom-free for 5 years. These two cases demonstrate that IFS can appear in a chronic variant form that is characterized by an indolent course and histologic evidence of tissue invasion by fungal hyphae. The type of treatment is dependent on the extent of the disease on initial examination and the rapidity of its progression.     

Use of Immunomatrix Methods to Improve Protein-Protein Interaction Detection

Immunoprecipitation (IP) and coimmunoprecipitation (co-IP) are keytechniques for studying protein-protein interactions. Thesemethods utilize immobilized protein A or protein G to isolateantibody-bound target antigens. The main disadvantage oftraditional immunoprecipitation and coimmunoprecipitation is thatthe conditions used to elute the precipitated antigen alsorelease the antibody, contaminating the antigen and destroyingthe antibody support. To overcome these problems, we describe twomethods to generate a reusable antibody support by cross-linkingthe antibody to immobilized protein A or protein G, or bycoupling it directly to the resin. Ourstudies have demonstrated that the immobilization efficiency forthe antibody coupling method was similar for several species ofantibody. Furthermore, we illustrate that using both methods ofantibody immobilization yields IP and co-IP results similar totraditional protocols but eliminates the antibody heavy and lightchains contamination.     

Molecular epidemiology of penicillin-resistant and ciprofloxacin-resistant Streptococcus pneumoniae in Canada

Eighty-nine penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae isolates were evaluated by serotyping and pulsed-field gel electrophoresis. Although penicillin-resistant isolates demonstrated considerable homogeneity, resistance to ciprofloxacin did not correlate with a reduction in genotypic variability. These results suggest that, unlike that of penicillin resistance, the spread of S. pneumoniae ciprofloxacin resistance in Canada is currently not attributable to clonal dissemination.     

Recurrent neck disease in oral cancer.

PURPOSE: The goals were to examine the clinical and pathologic features of patients who developed metastatic squamous cell carcinoma in the cervical lymph nodes after initial treatment and to identify any common patterns. PATIENTS AND METHODS: A retrospective analysis of 35 patients of varying initial tumor stage was performed. There were 18 patients who had an initial neck dissection and 17 patients whose neck was managed by a "watch and wait" policy. RESULTS: Recurrence frequently involved level II nodes, and extracapsular spread was invariably present. The time taken for recurrence to develop was the same in both groups of patients (15 months, P =.35), and the overall median survival time after recurrence was 18 months (12 to 25 months, 95% confidence interval). In 27 of 29 patients (93%) who had the primary tumor resected, the thickness of tumor was greater than 5 mm. CONCLUSION: Neck recurrence may represent residual disease; it has histologically unfavorable features and consequently a poor prognosis. The frequency of recurrence at level II emphasizes the need for meticulous dissection in this region, and tumor thickness needs to be considered in planning treatment of the clinically negative neck.     

A review and assessment of potential sources of ethnic differences in drug responsiveness

The International Conference on Harmonization (ICH) E5 guidelines were developed to provide a general framework for evaluating the potential impact of ethnic factors on the acceptability of foreign clinical data, with the underlying objective to facilitate global drug development and registration. It is well recognized that all drugs exhibit significant inter-subject variability in pharmacokinetics and pharmacologic response and that such differences vary considerably among individual drugs and depend on a variety of factors. One such potential factor involves ethnicity. The objective of the present work was to perform an extensive review of the world literature on ethnic differences in drug disposition and responsiveness to determine their general significance in relation to drug development and registration. A few examples of suspected ethnic differences in pharmacokinetics or pharmacodynamics were identified. The available literature, however, was found to be heterologous, including a variety of study designs and research methodologies, and most of the publications were on drugs that were approved a long time ago.     

Determining toxicity of lead and zinc runoff in soils: salinity effects on metal partitioning and on phytotoxicity

When assessing cationic metal toxicity in soils, metals are often added to soil as the chloride, nitrate, or sulfate salts. In many studies, the effects of these anions are ignored or discounted; rarely are appropriate controls included. This study used five soils varying in pH, clay content, and organic matter to determine whether salinity from counter-ions contributed to or confounded metal phytotoxicity. Varying rates of Pb and Zn were applied to soils with or without a leaching treatment to remove the metal counter-ion (NO3-). Lactuca sativa (lettuce) plants were grown in metal-treated soils, and plant dry weights were used to determine median effective concentrations where there was a 50% reduction in yield (EC50s) on the basis of total metals measured in the soil after harvest. In two of the five soils, leaching increased the EC50s significantly for Zn by 1.4- to 3.7-fold. In three of the five soils, leaching increased the EC50s significantly for Pb by 1.6- to 3.0-fold. The shift in EC50s was not a direct result of toxicity of the nitrate ion but was an indirect effect of the salinity increasing metal concentrations in soil solution and increasing its bioavailability for a given total metal concentration. In addition, calculation of potential salinity changes in toxicological studies from the addition of metals exhibiting strong sorption to soil suggested that if the anion associated with the metal is not leached from the soil, direct salinity responses could also lead to significant overestimation of the EC50 for those metals. These findings question the relevance of the application of single-metal salts to soils as a method of assessing metal phytotoxicity when, in many cases in our environment, Zn and Pb accumulate in soil over a period of time and the associated counter-ions are commonly removed from the soil during the accumulation process (e.g.. roof and galvanized tower runoff).     

Peritoneal dialysis fluid concentrations of linezolid in the treatment of vancomycin-resistant Enterococcus faecium peritonitis

OBJECTIVE: To determine linezolid concentrations in peritoneal dialysis fluid after multiple oral doses of the drug in a 46-year-old man with vancomycin-resistant Enterococcus faecium peritonitis who was undergoing peritoneal dialysis. METHODS: After administration of oral linezolid 600 mg twice/day was started, peritoneal dialysis fluid was collected at the end of several 4- and 8-hour dwell times and submitted for analysis of linezolid concentration. Before linezolid therapy was begun, and immediately after several peritoneal dialysis exchanges, 30 ml of expended peritoneal dialysis fluid was collected in a sterile container and immediately frozen at -70 degrees C until analysis by high-performance liquid chromatography. RESULTS: Peritoneal dialysis concentrations of linezolid greater than 4 microg/ml were achieved after the first dose of linezolid and maintained after repeated doses. During the course of therapy, mean linezolid concentrations in peritoneal dialysis fluid tended to increase (mean 7.60 pg/ml, range 3.54-16.2 microg/ml). All assayed peritoneal dialysis samples demonstrated linezolid concentrations greater than 4 microg/ml at the end of 4- or 8-hour dwell times, except for one level after a missed dose on linezolid treatment day 3. Duration of dwell times did not appear to correlate with linezolid concentrations. CONCLUSION: In this patient, linezolid 600 mg twice/day penetrated into peritoneal dialysis fluid at or above the concentrations necessary to treat common gram-positive bacteria. Linezolid therapy is likely to have a role in peritoneal dialysis-associated peritonitis based on its antimicrobial activity, pharmacokinetic properties, ease of administration, and tolerability.