European ST80 community-associated methicillin-resistant Staphylococcus aureus orbital cellulitis in a neonate

Background

To report atypical features on Spectral domain optical coherence tomography (SD-OCT) in a case of non-familial pure adult nanophthalmos.

Case presentation

A 39?year old male hyperope was found to have biometric and fundus findings typical of nanophthalmos. The additional atypical features included serous pigment epithelial detachment (PED) in right eye and a cuff of subretinal fluid with underlying yellow deposits along superotemporal arcade in the left eye. Fundus flourescein angiogram showed hyperfluorescence due to window defect, dye pooling due to serous PED in right eye and leak superior to disc in right eye and superotemporally in left eye. Cirrus-SD OCT horizontal line scan passing through the fovea showed extensive inner limiting membrane corrugations causing distorted foveal contour in both eyes. A large juxtafoveal serous PED and a small extrafoval PED were seen with folds in the retinal pigment epithelium (RPE)-choriocapillary layer in the right eye.

Conclusion

Structural disruptions in the RPE-choriocapillary complex in the form of folds or juxtafoveal serous PED and RPE folds can be atypical features of nanophthalmic macula better discerned on high resolution OCT.     

The X chromosome in Duchenne''s muscular dystrophy

A search for deficiencies on one X chromosome of four obligatory and four probable heterozygotes for Duchenne's muscular dystrophy was unsuccessful. This probably excludes deficiencies larger than half the width of any band or interband.     

Comparison of cotrimoxazole vs. second-generation cephalosporins for prevention of urinary tract infections in children

Background

Antimicrobial prophylaxis is recommended for the prevention of urinary tract infections (UTI) in high-risk children. However, there is growing concern about the use of β-lactams as prophylaxis and subsequent development of antibiotic resistance.

Methods

In this prospective, randomized, crossover controlled trial we compared cotrimoxazole (SXT) and second-generation cephalosporins (2GC) as UTI prophylaxis in children ranging in age from 1 to 60 months. Eligible patients were 1:1 randomized to receive either SXT or 2GC for the initial 6-month period (1 course), then switched to the other antimicrobial agent class for the subsequent course, with switching continuing after each course until the end of the study. Urethral orifice cultures (UOCs) were obtained at the time of switching antimicrobial prophylaxis.

Results

Among 97 children (mean age 13.6 months) on prophylaxis, breakthrough UTIs occurred during 13.3 % (10/75) of SXT courses and 10.3 % (8/78) of 2GC courses (p?=?0.62). 2GC failed earlier than SXT (mean?± standard error: 0.81?±?0.1 vs. 2.37?±?0.36 months, respectively; p?=?0.028). Pseudomonas aeruginosa and Enterococcus spp. were more frequently isolated after 2GC courses than after SXT courses [22.6 vs. 4.8 % (p?=?0.02) and 20.7 vs. 4.8 % (p?=?0.035), respectively]. Prophylaxis with 2GC significantly increased resistance to both 2GC and SXT, while SXT prophylaxis did not affect susceptibility to 2GC.

Conclusions

While SXT and 2GC appear to be equally efficacious as UTI prophylaxis in children, the latter exert a broader effect on patients’ flora and development of bacterial resistance, suggesting that SXT may be more appropriate for UTI prophylaxis than 2GC.

     

Pharmacokinetics and Concentration-Dependent Efficacy of Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis

We studied the pharmacokinetics and efficacy of the broad-spectrum triazole isavuconazole for the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Treatment started 24 h after endotracheal administration of Aspergillus fumigatus inoculum; study subjects included rabbits receiving orally administered prodrug isavuconazonium sulfate (BAL8557) equivalent to active moiety isavuconazole (ISA; BAL4815) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg (of body weight)/day, with an initial loading dose of 90 mg/kg (ISA90), and untreated rabbits (UC). There were significant concentration-dependent reductions of residual fungal burden (log CFU/gram) and of organism-mediated pulmonary injury, lung weights, and pulmonary infarct scores in ISA40- and ISA60-treated rabbits in comparison to those of UC (P < 0.001). ISA20-treated (P < 0.05), ISA40-treated, and ISA60-treated (P < 0.001) rabbits demonstrated significantly prolonged survival in comparison to that of UC. ISA40- and ISA60-treated animals demonstrated a significant decline of serum (1→3)-β-d-glucan levels (P < 0.05) and galactomannan indices (GMIs) during therapy following day 4 in comparison to progressive GMIs of UC (P < 0.01). There also were significantly lower concentration-dependent GMIs in bronchoalveolar lavage (BAL) fluid from ISA40- and ISA60-treated rabbits (P < 0.001). There was a direct correlation between isavuconazole plasma area under the concentration-time curve from 0 to 24 h (AUC_0–24) and residual fungal burdens in lung tissues, pulmonary infarct scores, and total lung weights. In summary, rabbits treated with isavuconazole at 40 and 60 mg/kg/day demonstrated significant dose-dependent reduction of residual fungal burden, decreased pulmonary injury, prolonged survival, lower GMIs in serum and BAL fluid, and lower serum (1→3)-β-d-glucan levels.     

Contribution of the CFTR gene, the pancreatic secretory trypsin inhibitor gene (SPINK1) and the cationic trypsinogen gene (PRSS1) to the etiology of recurrent pancreatitis

Acute recurrent/chronic pancreatitis (CP) is a complex multigenic disease. This is a case-control study consisting of 25 Greek patients with CP and a control population of 236 healthy Greek subjects. The whole coding area and neighboring intronic regions of the three genes were screened. Seventeen of 25 patients (68%) had mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: nine compound heterozygotes with either mild or severe mutations and eight heterozygotes. Four patients (16%) carried CFTR-modulating haplotypes V470-TG11-T5 and V470-TG12-T7. All were negative for PRSS1 gene mutations, while variants c.486C/T and c.738C/T were found in nine patients each, three homozygotes for the minor alleles. Two carried SPINK1 gene mutation p.N34S, one being transheterozygote with CFTR mutation p.F1052V. The promoter variant -253T>C was found in four individuals (one homozygous for the minor allele), all four being transheterozygotes with mutations in the CFTR gene as well. Finally two carried c.272C/T in the 3' untranslated region, one being a p.N34S carrier as well. In total, 80% (20/25) of patients had a molecular defect in one or both of the CFTR and SPINK1 genes, suggesting that mutations/variants in the CFTR plus or minus mutations in the SPINK1, but not the PRSS1 gene, may confer a high risk for recurrent pancreatitis.     

Dexamethasone as adjuvant therapy to moxifloxacin attenuates valve destruction in experimental aortic valve endocarditis due to Staphylococcus aureus

Although the beneficial effects of dexamethasone have frequently been investigated in various serious-infection settings, insufficient data on valve histology and cardiac function for infective endocarditis are available. The efficacy of moxifloxacin for the treatment of experimental aortic valve endocarditis due to methicillin-susceptible Staphylococcus aureus and the long-term effects of dexamethasone were evaluated in the current study. Sixty-eight rabbits were randomly assigned to four groups: A, B, C, and D. Group A consisted of 18 animals and functioned as a control group. Groups B and C consisted of 11 and 23 subjects, respectively, which received moxifloxacin for 5 days in a human-like pharmacokinetic simulation. Group D consisted of 16 animals that were administered moxifloxacin plus dexamethasone (0.25 mg/kg of body weight twice a day intravenously). The group B animals were sacrificed a day after the completion of treatment, and group C and D animals were sacrificed after 12 days in order to monitor any possible relapse and allow microbiological, histopathological, and echocardiographic evaluation of the long-term effects of glucocorticoids. No differences in survival, sterilization rates, or inflammatory infiltration and calcification of valve tissue were observed among the treated groups. However, the degrees of valve damage and collagenization were significantly worse, the fibroblast content was higher, and fractional shortening of the left ventricle fluctuated significantly in group C compared to group D (all groups, P < 0.05). We concluded that dexamethasone treatment for experimental S. aureus endocarditis attenuates valve destruction and preserves overall cardiac function without impeding the efficacy of moxifloxacin.     

On the management of hyperglycaemia in critically ill patients undergoing surgery

Hyperglycaemia is a major health risk and a negative determinant of surgical outcome. Despite its increasing prevalence, the limited treatments for restoration of normoglycaemia make its effective management a highly complex individualized clinical art. In this context, we review the mechanisms leading to hyperglycaemic damage as the basis for effective management of surgical complications of diabetic and non diabetic critically ill patients.     

Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece

In order to study whether the use of the heptavalent pneumococcal conjugate vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 2649 nasopharyngeal samples were obtained between 2005 and 2009, from children attending day-care centers in Central Greece. The percentage of attendees vaccinated with ≥1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non-PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the only PCV7 serotype that continued to circulate. A significant increase in the frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates coincided with a marked reduction in isolates with high resistance to penicillin. Several non-PCV7 serotypes colonized the children, but their frequency varied substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e. 6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted for ≥2% of pneumococcal isolates in at least 2 annual surveillances. An increase in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred. Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C, 15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive disease remains to be seen in the years ahead.     

Sequence-based genotyping HPV L1 DNA and RNA transcripts in clinical specimens

We developed a direct sequence-based genotyping method to detect single and multiple HPV L1 DNA and RNA types in genital and dermatological specimens. Our method couples PCR amplification of a highly conserved HPV L1 segment using a broad spectrum-generic primer cocktail mix with automated sequencing of amplified PCR products, followed by GenBank sorting of sequencing data. We genotyped 5 skin and 30 cervical HPV DNA-positive specimens using this method and established its first experimentally derived working cutoff value with the aid of commercial hybridization-based techniques. We suggest that sequence-based genotyping of appropriately amplified DNA and RNA products may serve as a primary HPV detection method in dermatological specimens. It can be applied as an all-purpose genotyping method for rare HPV types not detectable by commercial hybridization-based techniques and for sorting multiple HPV infections by order of prevalence.