Road Less Traveled: Drug Hypersensitivity to Fluoroquinolones, Vancomycin, Tetracyclines, and Macrolides.

While fluoroquinolones, vancomycin, macrolides, and tetracyclines are generally safe antibiotics, they can induce both immediate and delayed hypersensitivity reactions (HSRs). Historically, less has been published on allergies to these antibiotics compared to beta lactams, but the prevalence of non-beta lactam HSRs is increasing. To fluoroquinolones, immediate HSRs are more common than delayed reactions. Both IgE and non-IgE mechanisms, such as the mast cell receptor Mas-related G protein-coupled receptor X2 (MRGPRX2), have been implicated in fluoroquinolone-induced anaphylaxis. Skin testing for fluoroquinolones is controversial, and the gold standard for diagnosis is a graded dose challenge. To vancomycin, the most common reaction is vancomycin infusion reaction (previously called "red man syndrome"), which is caused by infusion rate-dependent direct mast cell degranulation. Severity can range from flushing and pruritis to angioedema, bronchospasm, and hypotension that mimic type I HSRs. MRGPRX2 has been implicated in vancomycin infusion reactions. IgE-mediated HSRs to vancomycin are rare. Vancomycin skin testing yields high false positive rates. Thus, direct provocation challenge with slower infusion rate and/or antihistamine pre-treatment is preferred if symptoms are mild to moderate, and desensitization can be considered if symptoms are severe. To tetracyclines, non-IgE-mediated and delayed HSRs predominate with cutaneous reactions being the most common. There is no standardized skin testing for tetracyclines, and avoidance is generally recommended after a severe reaction because of the paucity of data for testing. Graded dose challenges and desensitizations can be considered for alternative or index tetracyclines if there are no alternatives. With macrolides, urticaria/angioedema is the most common immediate HSR, and rash is the most common delayed HSR. The predictive value for skin testing to macrolides is similarly poorly defined. In general, HSRs to fluroquinolones, vancomycin, macrolides, and tetracyclines are challenging to diagnose given the lack of validated skin testing and in vitro testing. Direct provocation challenge remains the gold standard for diagnosis, but the benefits of confirming an allergy may not outweigh the risk of a severe reaction. Skin testing, direct provocation challenge, and/or desensitization to the index non-beta lactam antibiotic or alternatives in its class may be reasonable approaches depending on the clinical context and patient preferences.

Allergic Stomatitis From Orthodontic Adhesives.

We report a case of a type IV hypersensitivity reaction causing oral stomatitis, presumed to be the result of common dental adhesives. The case was diagnosed using patch testing to the dental adhesives that were used in the patient. Both of the adhesives tested contained a form of acrylate that is being seen more frequently in the literature as a cause of type IV hypersensitivity reactions. Metals can cause allergic reactions; however, other contact items need to be considered as a cause of oral allergic reactions. Cases of allergic stomatitis are rising and there is question if all-in-one adhesives may be contributing to this rise.

Impact of Immunoglobulin Therapy in Pediatric Disease: a Review of Immune Mechanisms.

Intravenous immunoglobulin (IVIG) provides replacement therapy in immunodeficiency and immunomodulatory therapy in inflammatory and autoimmune diseases. This paper describes the immune mechanisms underlying six major non-primary immunodeficiency pediatric diseases and the diverse immunomodulatory functions of IVIG therapy. In Kawasaki disease, IVIG plays a major, proven, and effective role in decreasing aneurysm formation, which represents an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. In immune thrombocytopenia, IVIG targets the underlying increased platelet destruction and decreased platelet production. Although theoretically promising, IVIG shows no clear clinical benefit in the prophylaxis and treatment of neonatal sepsis. Limitations in research design combined with the unique neonatal immunologic environment offer explanations for this finding. Inflammation from aberrant immune activation underlies the myelinotoxic effects of Guillain-Barré syndrome. HIV-1 exerts a broad range of immunologic effects and was found to decrease serious bacterial infections in the pre-highly active anti-retroviral therapy (HAART) era, although its practical relevance in the post-HAART era has waned. Clinical and experimental data support the role of immune mechanisms in the pathogenesis of childhood epilepsy. IVIG exerts anti-epileptic effects through targeting upregulated cytokine pathways and antibodies thought to contribute to epilepsy. Applications in six additional pediatric diseases including pediatric asthma, atopic dermatitis, cystic fibrosis, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), autism, and transplantation will also be briefly reviewed. From autoimmunity to immunodeficiency, a dynamic immunologic basis underlies major pediatric diseases and highlights the broad potential of IVIG therapy.

Isolation of bacterial cerebrospinal fluid culture contaminants at a major military medical center.

In recent decades, bacterial meningitis rates have decreased secondary to the success of routine vaccinations. Ironically, the decreased incidence may contribute to the challenge of establishing accurate and timely diagnoses. Studies have suggested that in immunocompetent patients with normal cerebrospinal fluid (CSF) white blood cell counts (WBC), positive CSF cultures may be disregarded as presumed contaminants, making the initial CSF WBC increasingly relevant. This single-institution retrospective study sought to integrate clinical data with positive cultures in an era when CSF contaminants may be more commonly isolated in culture than true pathogens. A total of 7715 adult and pediatric CSF samples from 1995 to 2009 were obtained at a major military medical center. Clinical and laboratory data from 121 positive bacterial cultures were reviewed. Our bacterial CSF contamination rate (false positives) was 0.91% (70/7715). True-positive (TP) CSF cultures totaled 51 (0.66%). Among TPs, 16% (8/51) demonstrated normal CSF cell counts. The notably low 15-year CSF contamination rate of 0.91%, suggests that positive cultures are likely to represent true infection in our institution. We believe efforts to decrease the contamination rate are among the most cost-effective, while targeted clinical re-evaluation for all patients with positive CSF cultures remains vital. In light of this data, a targeted approach to re-evaluating positive cultures while incorporating the clinical context remains prudent.

A comparison study of different PCR assays in measuring circulating plasma epstein-barr virus DNA levels in patients with nasopharyngeal carcinoma.

PURPOSE: To compare the performance of three PCR assays in measuring circulating Epstein-Barr virus (EBV). DNA levels in nasopharyngeal carcinoma patients and to confirm its prognostic significance. EXPERIMENTAL DESIGN: Plasma from 58 newly diagnosed nasopharyngeal carcinoma patients were collected before, during, and every 3 to 6 months after radiotherapy. EBV DNA levels were determined by real-time quantitative PCR using primer/probe sets for polymerase-1 (Pol-1), latent membrane protein 2 (Lmp2), and BamHI-W. Pretreatment levels from the three assays were correlated with each other and serial measurements from the Pol-1 assay were correlated with clinical variables. RESULTS: Pol-1 was more accurate than BamHI-W in predicting EBV DNA concentrations in cell lines. Of the three assays, BamHI-W yielded the highest concentrations followed by Pol-1 in plasmas (n = 23). The correlation coefficient was 0.99 (P < 0.0001) for Pol-1 and Lmp2, 0.66 (P < 0.0001) for Pol-1 and BamHI-W, and 0.55 (P < 0.0001) for BamHI-W and Lmp2. Elevated pretreatment DNA levels as detected by Pol-1 were correlated with advanced nodal stage (P = 0.04) and overall stage (P = 0.028). There was no correlation between pretreatment EBV DNA levels and freedom-from-relapse or overall survival; however, there was a significant correlation between posttreatment levels and these variables. The 2-year freedom-from-relapse and overall survival rates were 92% and 94% for patients with undetectable, and 37% and 55% for those with detectable, posttreatment levels (P < 0.0001 and P < 0.002). CONCLUSIONS: The three PCR assays yielded similar results in detecting EBV DNA in plasmas. The Pol-1-detected posttreatment EBV DNA level was the strongest predictor for treatment outcomes.