Identification and Antimicrobial Susceptibility of Alcaligenes xylosoxidans Isolated from Patients with Cystic Fibrosis

In the past decade, potential pathogens, including Alcaligenes species, have been increasingly recovered from cystic fibrosis (CF) patients. Accurate identification of multiply antibiotic-resistant gram-negative bacilli is critical to understanding the epidemiology and clinical implications of emerging pathogens in CF. We examined the frequency of correct identification of Alcaligenes spp. by microbiology laboratories affiliated with American CF patient care centers. Selective media, an exotoxin A probe for Pseudomonas aeruginosa, and a commercial identification assay, API 20 NE, were used for identification. The activity of antimicrobial agents against these clinical isolates was determined. A total of 106 strains from 78 patients from 49 CF centers in 22 states were studied. Most (89%) were correctly identified by the referring laboratories as Alcaligenes xylosoxidans. However, 12 (11%) strains were misidentified; these were found to be P. aeruginosa (n = 10), Stenotrophomonas maltophilia (n = 1), and Burkholderia cepacia (n = 1). Minocycline, imipenem, meropenem, piperacillin, and piperacillin-tazobactam were the most active since 51, 59, 51, 50, and 55% of strains, respectively, were inhibited. High concentrations of colistin (100 and 200 microg/ml) inhibited 92% of strains. Chloramphenicol paired with minocycline and ciprofloxacin paired with either imipenem or meropenem were the most active combinations and inhibited 40 and 32%, respectively, of strains. Selective media and biochemical identification proved to be useful strategies for distinguishing A. xylosoxidans from other CF pathogens. Standards for processing CF specimens should be developed, and the optimal method for antimicrobial susceptibility testing of A. xylosoxidans should be determined.     

Four mutations (three novel, one founder) in TACSTD2 among Iranian GDLD patients

PURPOSE: To perform a mutation screening of TACSTD2 in 13 Iranian Gelatinous Drop-like Corneal Dystrophy (GDLD) pedigrees. To assess genotype-phenotype correlations. To determine intragenic SNP haplotypes associated with the mutations, so as to gain information on their origin. METHODS: The coding region of TACSTD2 was sequenced in the probands of 13 unrelated Iranian GDLD pedigrees. Variations were assessed in other available affected and unaffected family members and in unrelated normal control subjects by restriction fragment length polymorphism (RFLP). The variations were classified as being associated with disease if they segregated with the disease phenotype in the families, were not observed in 100 control individuals, disrupted protein expression, or affected conserved positions in the coded protein. Three intragenic single-nucleotide polymorphisms (SNPs) were used to define haplotypes associated with putative disease-causing mutations. RESULTS: The probands were each homozygous for one of four putative disease-causing variations observed in TACSTD2: C66X, F114C, L186P, and E227K. Three of these are novel. E227K was found in 10 of the Iranian patients. There were some phenotypic differences among different patients carrying this mutation-for example, with respect to age at onset. Genotyping of intragenic SNPs identified four haplotypes. C66X, F114C, and L186P were each associated with a haplotype common among control chromosomes, whereas all E227K alleles were associated with a haplotype not found among the control chromosomes. CONCLUSIONS: Although mutations in TACSTD2 among Iranian patients with GDLD were heterogeneous, E227K was found to be a common mutation. It is suggested that E227K may be a founder mutation in this population. Based on positions of known mutations in TACSTD2, significance of the thyroglobulin domain of the TACSTD2 protein in the pathogenesis of GDLD is suggested.     

Ethambutol neuroretinopathy

OBJECTIVE: To describe the clinical features of ethambutol neuroretinopathy. DESIGN: Case report and meta-analysis of the literature. PARTICIPANTS: A patient with clinical and electrophysiological findings suggestive of ethambutol neuroretinopathy. TESTING: Electroretinogram, electro-oculogram and visual fields. MAIN OUTCOME MEASURE: Clinical and electrophysiological findings. RESULTS: 101 cases were reviewed, retinal findings include retinal pigment epithelial changes, macular edema, flame-shaped hemorrhages. Electroretinogram findings include decreased amplitude and abnormal wave pattern in full field ERG, multifocal or pattern ERG and electro-oculogram findings include abnormal Arden ratio. CONCLUSIONS: Clinical, electrophysiological and in vitro studies support the toxic effect of ethambutol on the retina. Therefore ethambutol ocular toxicity may be a neuroretinopathy.     

Diagnostic accuracy of IL-2 for the diagnosis of latent tuberculosis: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarkers for the diagnosis of latent tuberculosis. Related studies were identified through searches of PubMed, Embase, Web of Science, and complementary manual searches up to December 30, 2013. We used standard methods recommended for meta-analyses of diagnostic test evaluations. The analysis was based on a summary receiver operating characteristic (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of the meta-analysis. The potential presence of publication bias was tested using the Deeks’ funnel plots. The pooled estimates of IL-2 for latent tuberculosis infection (LTBI) diagnosis were as follows: sensitivity, 0.81 [95 % confidence interval (CI), 0.60 to 0.92]; specificity, 0.95 (95 % CI, 0.90 to 0.97); positive likelihood ratio (PLR), 15.2 (95 % CI, 8.1to 28.4); negative likelihood ratio (NLR), 0.20 (95 % CI, 0.09 to 0.47). We found that the SROC curve is positioned near the upper left corner of the curve and the area under the curve (AUC) was 0.96 (95 % CI, 0.94 to 0.98). In conclusion, according to the meta-analysis, IL-2 is a valid marker for the diagnosis of LTBI. When there is no definite gold standard for the diagnosis of LTBI, IL-2 release assay in addition to interferon-gamma release assays (IGRAs) can improve the ability of IGRAs to identify individuals with LTBI.     

The influence of human leukocyte antigen and IL-10 gene polymorphisms on hepatitis B virus outcome

Context

The clinical outcome of hepatitis B virus (HBV) infection is variable, ranging from spontaneous recovery to an inactive carrier state, chronic hepatitis, occult HBV infection, liver cirrhosis, or hepatocellular carcinoma.

Evidence Acquisition

This variable pattern and clinical outcomes of the infection were mainly determined by virological and host genetic factors. Since the most of host genetic factors associated with HBV infection have currently focused on human leukocyte antigen (HLA) associations and interleukin (IL)-10 gene polymorphisms, this review focuses on the recent progresses in these issues to provide prognostic markers for the outcome of HBV infection.

Results

A study on serum levels of IL-10 in occult HBV infected patients reported that the higher level of IL-10 production may suppress function of the immune system against HBV in patients with occult HBV infection. IL-10 promoter polymorphism at position -592 is associated with susceptibility to occult HBV infection.

Conclusions

Findings of this study suggest that the host HLA polymorphism is an important factor in determining outcome of HBV infection but regarding IL-10 gene promoter polymorphisms, we are still have a long way to achieve a definite conclusion.     

Fever and Psychosis as an Early Presentation of Brucella-Associated Meningoencephalitis: A Case Report

Objective

To describe a case with Brucella-associated meningoencephalitis. In addition, we report drug-induced hepatotoxicity due to acyclovir.

Clinical Presentation and Intervention

A young woman was admitted with fever and psychosis and neuroimaging findings indicative of meningoencephalitis. Serology was positive for Brucella. She was treated with doxycycline, rifampin, and trimethoprim-sulfamethoxazole.

Conclusion

This case reminds physicians in endemic regions to consider neurobrucellosis as a differential diagnosis in patients with any unexplained neurologic symptoms or atypical psychosis. Early diagnosis and treatment of neurobrucellosis will be helpful in decreasing the sequelae of this complication.Key Words: Brucellosis, Meningoencephalitis, Psychosis, Acyclovir, Hepatotoxicity