Maskit Bar-Meir

Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

SUMMARY A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis.

Type III Secretion Phenotypes of Pseudomonas aeruginosa Strains Change during Infection of Individuals with Cystic Fibrosis

ABSTRACT Pseudomonas aeruginosa is a frequent cause of respiratory exacerbations in individuals with cystic fibrosis. An important virulence determinant of this pathogen is its type III protein secretion system. In this study, the type III secretion properties of 435 P. aeruginosa respiratory isolates from 56 chronically infected individuals with cystic fibrosis were investigated. Although it had been previously reported that 75 to 90% of P. aeruginosa isolates from patients with hospital-acquired pneumonia secreted type III proteins, only 12% of isolates from cystic fibrosis patients did so, with nearly all of these isolates secreting ExoS and ExoT but not ExoU. Despite the low overall prevalence of type III protein-secreting isolates, at least one secreting isolate was cultured from one-third of cystic fibrosis patients. Interestingly, the fraction of cystic fibrosis patient isolates capable of secreting type III proteins decreased with duration of infection. Although 90% of isolates from the environment, the presumed reservoir for the majority of P. aeruginosa strains that infect patients with cystic fibrosis, secreted type III proteins, only 49% of isolates from newly infected children, 18% of isolates from chronically infected children, and 4% of isolates from chronically infected adults with cystic fibrosis secreted these proteins. Within individual patients, isolates of clonal origin differed in their secretion phenotypes, indicating that as strains persisted in cystic fibrosis patient airways, their type III protein secretion properties changed. Together, these findings indicate that following infection of cystic fibrosis patient airways, P. aeruginosa strains gradually change from a type III protein secretion-positive phenotype to a secretion-negative phenotype.

Evolution of Pseudomonas aeruginosa type III secretion in cystic fibrosis: a paradigm of chronic infection

Pseudomonas aeruginosa (PA) from acute and chronic (eg, cystic fibrosis (CF)) infections differ in several respects, but they can worsen prognosis in each context. Factors that facilitate conversion from an acute to chronic phenotype are poorly understood. T3 secretion proteins are virulence factors associated with poorer outcomes in acute infections, but little is known about their role in CF. We wished to characterize T3 secretion in CF PA isolates and to examine its role in clinical outcomes. A total of 114 CF subjects were divided into 3 cohorts: 1st infected individuals, CI children, and adults. Serial respiratory cultures were analyzed for T3 secretion. Serial spirometry and exacerbation data were collected prospectively. In 1st infection, 45.2% +/- 9.1% of PA isolates secreted T3 proteins compared with 29.1% +/- 4.2% and 11.5% +/- 3.0% in CI children and CI adults, respectively (P < 0.001). An inverse correlation was observed between duration of PA infection and percent T3 positive isolates (r = -0.32, P < 0.001). Overall, no association was observed between T3 secretion and pulmonary outcomes, but in the subgroup of subjects who had at least 1 T3 positive organism, T3 secretion was inversely correlated with the forced expiratory volume in 1 s (FEV(1)) decline (r = -0.35, P = 0.02). In 1st infection, 82% of cultures grew either all or no T3-positive organisms. In these patients, T3 secretion was associated with a greater risk of subsequent PA isolation (P < 0.001). In CF, PA T3 secretion decreases with residence time in lung, may predict FEV(1) decline in patients who have detectable T3 organisms, and may facilitate persistence after 1st infection.

Kawasaki disease in Israel.

Objective: To characterize the epidemiology and estimate the incidence of Kawasaki disease (KD) among children in Israel. Methods: Using the Israel National Hospital Discharge Register, we investigated the epidemiologic features of KD among children <18 years of age between 1996 to 2009 in Israel. Incidence rates were calculated using the corresponding census data. Results: During 1996 through 2009, 685 children <18 years of age were hospitalized for KD in Israel. Of these children, 88% were aged <5 years; the male/female ratio was 1.7:1; and most cases occurred in late winter-early spring. The overall incidence of KD was 6.4 per 100,000 children <5 years of age. Since 2000, there was a gradual increase in KD incidence as well as in the ratio of KD-associated hospitalizations to all-cause pediatric hospitalizations. For male infants <1 year of age, KD rates almost doubled: from 5.8 per 100,000 cases in 1996–1998 to an average of 11.9 cases per 100,000 in the following years (P = 0.002). The overall proportion of patients with coronary artery aneurysm was 2.9%, higher rates of coronary artery aneurysm were observed in patients <1 or >5 years of age and in male patients. Conclusions: Major epidemiologic features of KD among Israeli children are similar to those reported for the white population in Europe and the United States. KD incidence increased during the study period, especially among male infants <1 year of age.

A prospective controlled trial of the optimal volume for neonatal blood cultures.

Background: Bacteremia is a frequent complication in neonatal intensive care units. Blood cultures are the standard for the diagnosis. It is a common practice to draw small blood volumes for culture from neonates in order to prevent anemia; however, this might compromise the test sensitivity. We examined whether using 1 mL of blood in a single aerobic bottle would improve the culture yield compared with our current practice of obtaining 2 samples of 0.5 mL of blood (aerobic and anaerobic bottles). Methods: A prospective controlled study was conducted between December 2009 and September 2010 at the neonatal intensive care unit of Shaare Zedek Medical Center, Jerusalem, Israel. Study population included newborns from whom blood cultures were obtained. A sample of 2 mL of blood from each patient was divided into a single aerobic bottle (1 mL; study sample) and into 2 aerobic and anaerobic bottles (0.5 mL each; control samples). Culture bottles were weighed before and after blood inoculation and time to positivity (TTP) was recorded. Results: We obtained 706 complete culture sets from 519 patients. Pathogens grew in 72 (10.2%) cultures from 37 patients. Isolation of organisms was significantly higher in the 0.5 mL control group (94.4% vs. 77.7%, P = 0.012). The TTP was similar in 0.5 mL and 1 mL aerobic bottles, but significantly longer in the anaerobic bottle. Conclusions: Allocating 1 mL of blood into 2 bottles, aerobic and anaerobic, improved the yield of the culture compared with 1 mL in a single aerobic bottle.

Staphylococcus aureus Skin and Soft Tissue Infections: Can We Anticipate the Culture Result?

This prospective study was designed to evaluate predictors of skin and soft tissue infections (SSTI) due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Consecutive patients who were hospitalized with S aureus SSTI were enrolled. CA-MRSA infection was diagnosed in 76% of the children. MRSA SSTI was associated with black race (P = .0001) and with infection involving the lower trunk (P = .008). Only 21% of the patients in this study had S aureus colonization in their nares, and in 3 cases there was discordance between the nares and the infection site cultures. Sensitivity, specificity, and predictive values of the risk factors examined were limited in their ability to predict CA-MRSA infection. Given the high prevalence of MRSA in our community and the inability of nasal cultures to reliably predict CA-MRSA infection, empirical antibiotic therapy active against CA-MRSA and contact isolation of patients are recommended.

Catheter-related fungemia due to Candida thermophila

ABSTRACT We report a case of bloodstream infection caused by Candida thermophila, a yeast not previously associated with human disease. The infection occurred in a 13-year-old boy with medulloblastoma who presented with 1 day of fever. Multiple blood cultures were positive for yeast. Removal of the catheter resulted in prompt resolution of the fever and sterilization of the blood cultures. The species was identified by sequencing domains 1 and 2 of the large subunit rRNA gene. Antifungal susceptibility testing was also performed.

Does Acute Otitis Media in the First Month of Life Increase the Risk for Recurrent Otitis

Acute otitis media (AOM) is a common childhood illness. The aim of this study was to assess whether AOM in the first month of life predicts recurrent AOM (rAOM) in early childhood. The medical records of all neonates with AOM and isolation of bacterial pathogen from middle-ear fluid during 2005-2010 were reviewed. Neonates without AOM admitted during the same period for neonatal fever workup were included as controls. Information regarding rAOM and possible risk factors were collected through a phone interview with the parents. A total of 84 neonates with AOM were enrolled; 25 (30%) had rAOM compared with 8/79 (10%) in the control group. Neonatal AOM increases 4-fold the odds of rAOM later in childhood (odds ratio = 4; 95% CI = 1.44-11.42; P = .008), independent of smoke exposure, numbers of siblings, AOM in siblings, breastfeeding, day care attendance, or use of pacifier. Neonatal AOM is a significant risk factor for rAOM during infancy.