Pharmacotherapy Approaches in Nontuberculous Mycobacteria Infections

Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.     

Microbiologic diagnosis of community-acquired pneumonia in adults

Microbiological analysis allows us to identify the etiology of pneumonia and its in vitro susceptibility pattern. Antibiotic treatment directed against a known pathogen enables us to narrow antibacterial spectrum of action, and to reduce costs, drug adverse effects risk and antibiotic resistance. However it is unnecessary to perform extended microbiological studies in all patients with community acquired pneumonia (CAP). Etiological studies must be based in pneumonia severity, epidemiological risk factors and clinical response to empirical treatment. Routine microbiological analysis for ambulatory patients is not recommended. In patients with persistent cough and worsening in their general conditions, a sputum sample must be obtained to perform an acid-fast smear and Mycobacterium culture. The risk of complications and death of patients hospitalized with CAP justifies basic microbiological exploration (sputum Gram staining and culture, blood cultures, pleural fluid culture) intending to obtain a more accurate etiology of pulmonary infection and to guide specific antibiotic treatment. Paired serum samples obtained to document atypical pathogen infections (Mycoplasma pneumoniae, Chlamydia pneumoniae) and urine sample to detect Legionella pneumophila antigenuria are recommended in all CAP severely ill patients that are admitted to ICU, in those not responding to betalactamic drug treatment and in selected patients with specific epidemiological risks. A microbiological study would be useful in management of patients with severe CAP pneumonia outbreaks with clinical-epidemiological particular characteristics, and in-patients with empirical antimicrobial treatment failure.     

Resident participation and postoperative outcomes in adrenal surgery

Background

The changing paradigm of surgical residency training has raised concerns about the effects on the quality of training. The purpose of this study is to identify if resident participation in laparoscopic adrenalectomy (LA) and open adrenalectomy (OA) cases is associated with deleterious outcomes.

Materials and methods

This is a retrospective study using the American College of Surgeons National Surgical Quality Improvement Program database. Data from patients undergoing LA and OA from 2005 to 2010 were queried. Preoperative variables as well as intra- and post-operative outcomes for each procedure were evaluated. Multivariate logistic regression was used to analyze if resident participation was associated with significant differences in outcomes, compared with no resident participation. Subset analysis was done to determine possible differences in outcomes based on the level of resident participating, divided into junior (Post Graduate Year [PGY]1–3), senior (PGY4–5), or fellow (≥PGY6) levels.

Results

A total of 3219 adrenalectomies were performed. Of these, 735 (22.8%) were OAs and 2484 (77.2%) were LAs. Residents were involved in 2582 (80.2%) surgeries, which comprised 1985 (76.9%) LAs and 597 (23.1%) OAs. Senior residents or fellows performed majority of the cases (85.2%). Mean operative time was significantly higher with resident participation in LA (P < 0.0001) and OA group (P < 0.0001). On multivariate analysis, resident participation was not associated with significant differences in the operative outcomes of 30-d mortality or postoperative complications after laparoscopic or OA.

Conclusions

Although resident participation does increase operative time in LA and OA, this does not appear to be clinically significant and does not result in adverse patient outcomes.     

Restoration of humeral head geometry in posttraumatic fracture sequelae with stemless or resurfacing arthroplasty: a matched-paired analysis

Background

The objective of this study was to analyze proximal humeral geometry in two groups of patients with posttraumatic fracture sequelae who were treated with either resurfacing (R) or stemless (S) arthroplasty. The hypothesis was that there is no difference in the radiographic restoration of postoperative proximal humeral geometry after resurfacing or stemless arthroplasties.

Material and methods

A match-paired analysis of 48 cases was completed (R?=?24, S?=?24). Proximal geometry was assessed reviewing true anterior–posterior x-rays, measuring the inclination angle of osteotomy (IAO), distance above tuberosity (DAT), superior humeral translation (SHT) according to Torchia, medial offset (MO), and lateral offset (LO).

Results

The average follow-up was 32.4?±?9.2 months for group R and 37.9?±?22.9 months for group S (p?=?0.317). Except for MO and SHT, no significant differences were found. Restoration of the anatomical MO was more accurate for group S. SHT of the humerus was detected more frequently for group R.

Conclusions

In this match-paired analysis, stemless arthroplasty reconstructed an anatomic MO more consistently than resurfacing arthroplasty as evaluated on x-rays; we did not document differences in the remaining evaluated parameters. However, no significant differences were found between both groups regarding clinical outcomes.     

Regional brain metabolism in a murine systemic lupus erythematosus model

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood–brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb− mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb− mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.