Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis. Methods: Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997-2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley -test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis. Results: Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4-4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5-15.9] and 3.2 [0.7-14.7], respectively. Conclusions: We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram -negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period

Therapeutic Effect of a Novel Oxazolidinone, DA-7867, in BALB/c Mice Infected with Nocardia brasiliensis

Actinomycetoma is an infectious disease of tropical and subtropical regions produced by actinobacteria of the genera Nocardia, Streptomyces, and Actinomadura. Therapeutic alternatives are scarce and include trimethoprim-sulfamethoxazole, diaminodiphenylsulfone, amoxicillin-clavulanate, imipenem, and amikacin. Oxazolidinones are a new class of antimicrobials with a completely different cellular target; the first compound in the market, linezolid, was introduced in the year 2000. It is active against many species of Nocardia and other aerobic actinomycetes; however, the long-term application in human subjects produces side effects including peripheral neuropathy and mielossupression. Therefore, it is important to screen other oxazolidinones with higher activity and less toxicity. In the present work, we tested DA-7867, a new oxazolidinone, in an experimental mouse model. The drug is active in vivo and decreases the production of lesions using only one dose a day in contrast to linezolid, which needs to be injected three times a day. Although it was tested on N. brasiliensis, it can possibly be active (once it is accepted for its use in humans) against Actinomadura spp and Streptomyces spp, which are frequently found in places of Africa and India where actinomycetoma is also an important consult in dermatology

Efficacy of CG 3 R 6 TAT Nanoparticles Self-Assembled from a Novel Antimicrobial Peptide for theTreatment of Candida albicans Meningitis in Rabbits

Background: Candidal meningitis is a common clinical manifestation of invasive candidiasis in neonates. The aim of this study was to evaluate the in vivo antifungal efficacy of CG3R6TAT nanoparticles, novel core-shell structures self-assembled from cationic antimicrobial peptides, in a rabbit model of candidal meningitis. Methods: In vitro activity of CG3R6TAT nanoparticles against Candida albicans was assessed by determining the minimum inhibitory concentration and kill-time curves. In vivo, intravenous treatment with CG3R6TAT nanoparticles (n = 6; 0.25 mg/kg/day) or fluconazole (n = 6; 100 mg/kg/day) began 3 days after infection and continued for 11 consecutive days; the efficacy was assessed following 11 days of treatment by yeast counting in cerebrospinal fluid (CSF), the leukocyte concentrations in CSF and the histopathology of brain parenchyma. Results: At a concentration three times higher than the minimum inhibitory concentration (8.1 µmol/l), the nanoparticles completely sterilized C. albicans after 5 h of incubation. In addition, there was a significant reduction in fungal counts and leukocyte concentrations in the CSF from rabbits treated with CG3R6TAT nanoparticles or fluconazole versus those from untreated control rabbits (p 0.05, vs. control). The histopathologic severity of rabbits was significantly attenuated after CG3R6TAT treatment (p = 0.001, vs. control). Conclusion: This study suggests that CG3R6TAT nanoparticles may be a promising therapeutic agent for candidal meningitis

Genetic diversity and antimicrobial susceptibility of Nocardia species among patients with nocardiosis

The aim of this multicenter study was to determine the genetic diversity and antibiotic susceptibility of clinically isolated Nocardia species. One hundred twenty-seven patients with nocardiosis were randomly selected from 5 provinces of Iran. Molecular diagnosis of Nocardia species was performed using multilocus sequence analysis of gyrase B of the β subunit of DNA topoisomerase (gyrB), and 16S rRNA and subunit A of SecA preproteintranslocase (secA1). Antimicrobial susceptibility testing was performed following the Clinical and Laboratory Standards Institute recommendations. Thirty-five N. cyriacigeorgica, 30 N. asteroides, 26 N. farcinica, 12 N. otitidiscaviarum, and 10 N. abscessus cultures were studied. All isolates were susceptible to linezolid. All isolates of N. cyriacigeorgica, N. asteroides, N. abscessus, and N. otitidiscaviarum were susceptible to trimethoprim-sulfamethoxazole, while 8% of N. farcinica isolates were resistant to this drug. All N. otitidiscaviarum isolates were highly resistant to imipenem, but N. cyriacigeorgica, N. asteroides, N. farcinica, and N. abscessus were only moderate resistant. The susceptibility patterns vary with different species of Nocardia. Resistance to trimethoprim-sulfamethoxazole in Iran is low and this drug should be first line therapy, unless drug susceptibility testing shows resistance. Linezolid also covers Nocardia well and could be a second line agent