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We sought here to investigate the patterns of Staphylococcus aureus carriage in the first year of life, its determinants, and the dynamics of transmission between mothers and infants. A prospective longitudinal cohort study of S. aureus carriage among mothers and their infants was performed, including monthly screenings from pregnancy/birth through the first year of the infant's life. Medical and lifestyle data were collected. Infant S. aureus carriage was detected from rectal and nasal swabs, and maternal carriage was detected from nasal and vaginal swabs. Multivariate analysis and a nonlinear mixed model (NLMIXED) were used to determine the predictors of carriage and S. aureus persistence. Of the 671 women recruited, 130 women carried S. aureus at recruitment (19.3%); they and their 132 infants were included in the study. A total of 93% of the infants acquired S. aureus sometime during the first year of life; 64% of these infants acquired the maternal strain, mostly (66%) during the first month of life. We observed that 70 women (52.50%) and 17 infants (14%) carried S. aureus persistently. Early acquisition of S. aureus carriage was associated with longer duration of initial carriage and was the most significant predictor of S. aureus persistence, while day care center attendance was negatively associated with persistent carriage. Methicillin-resistant S. aureus was carried by two infants for only 1 month each and not by any of the mothers. Early acquisition of S. aureus , mostly from the mother, is thus an important determinant of carriage persistence in infancy., (Copyright © 2019 American Society for Microbiology.)

Staphylococcus aureus is a pathogen that causes significant morbidity and mortality. Nasal carriage is a major source of transmission and of endogenous infection. Persistent carriage is detected in ∼30% of healthy individuals. While Th17 cells have been shown to play a role in S. aureus infection and clearance, the immune response to carriage is not well understood. Here, we evaluate the Th17 response and its potential inhibitors during S. aureus carriage. We recruited 25 volunteers, of whom 11 were persistent carriers. Volunteers' peripheral blood mononuclear cells (PBMCs) were stimulated with either their endogenous strain (a strain isolated from that carrier) or exogenous ones (strains not carried by that volunteer). Changes in Th17 cell frequency and numbers, interleukin-17 (IL-17) mRNA expression, and IL-17 protein abundance were measured by fluorescence-activated cell sorting, real-time PCR, and enzyme-linked immunosorbent assay. Similarly, responses of IL-17 suppressors (regulatory T cells [FOXP3], IL-10, IL-27, and IL-19) were measured. Th17 and IL-17 levels in response to stimulation with endogenous strains were significantly lower than those in response to stimulation with exogenous ones. Of the suppressive cytokines tested, only IL-19 exhibited a stronger response to endogenous than to exogenous strains. Addition of recombinant IL-19 to exogenous-strain-stimulated PBMCs caused decreased IL-17 expression, whereas addition of IL-19 antibodies to endogenous-strain-stimulated cells resulted in an increased IL-17 response. Together, our results suggest that S. aureus carriage induced a tolerogenic response to a carried strain that could be reproduced through the addition of recombinant IL-19 or prevented by the addition of IL-19 antibodies. This differential immune response may play a role in the determination of S. aureus carriage patterns., (Copyright © 2018 American Society for Microbiology.)

Background: Little is known about neonatal Staphylococcus aureus carriage. Sites and clinical outcomes of S. aureus colonization during the first month of life were evaluated in this study., Methods: A cohort of 279 infants born at term to 277 mothers was included. Maternal S. aureus colonization status was examined before labor. Newborns were screened for nasal, auricular, umbilical, and rectal colonization, one to three times within 100h after birth, and infants of carrier mothers were re-screened at 1 month. Medical data were recorded from the medical charts at discharge and at the 1-month follow-up interview., Results: Overall 43 out of 279 (15.4%) infants acquired S. aureus within the first days of life. The only two predictors of S. aureus carriage in the postnatal period were maternal S. aureus carriage (odds ratio 7.905, 95% confidence interval 3.182-19.638) and maternal antibiotic treatment during labor (odds ratio 0.121, 95% confidence interval 0.016-0.949). Among colonized children, the nose (56%) and rectum (40%) were more frequently colonized, while ear (26%) and umbilicus (16%) colonization were less common. Co-colonization at two sites was rare (4%), but always predicted carriage at 1 month of age. Maternal and neonatal characteristics, including neonatal outcomes, were similar between S. aureus carrier and non-carrier infants during the first month of life., Conclusions: Maternal carriage is the major predictor of neonatal S. aureus carriage. The nose and rectum are the main sites of neonatal carriage. S. aureus carriage was not associated with neonatal complications throughout the first month of life. The long-term significance of early S. aureus carriage is yet to be determined., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

It is not clear if patients with heterogeneous intermediate resistance to vancomycin (hVISA) infectious endocarditis (IE) differ from methicillin-resistant S. aureus (MRSA) IE patients. All cases of hVISA and MRSA IE diagnosed at the Sheba Medical Centre from 2003 to 2010 were included. Isolates were screened prospectively for hVISA. Medical records were reviewed. The t-test, chi-square test, Fisher exact test and Kaplan Meier analysis were used. Fourteen hVISA IE and 32 MRSA IE were identified. The mean age was 76 years, mean Charlson score was 4.5 and 24% of patients had prosthetic valves. Pacemakers and implantable cardioverter-defibrillators (P/ICDs) were more common in the hVISA group (50% vs. 22%, p 0.05). P/ICDs IE occurred in 29% of hVISA patients vs. 6.3% of MRSA patients (p 0.06). hVISA patients had more positive blood cultures (eight vs. five, p 0.007) and a trend toward longer bacteraemia (15 vs. 7.5 days, p 0.08). Vancomycin minimal inhibitory concentrations (MICs) were similar in the two groups (1.5 μg/mL vs. 1.1 μg/mL, p 0.11). The MIC to daptomycin was higher in hVISA (0.75 μg/mL vs. 0.32 μg/mL, p 0.049). MRSA patients received vancomycin. hVISA patients were switched to other antibiotics. Cardiac surgery and/or P/ICD extraction was performed more commonly in hVISA patients (50% vs. 16%, p 0.027). Mortality was high in both groups (57-66%). The median time to death was 39 days in the hVISA group and 19 days in the MRSA group (p 0.3). hVISA IE is associated with P/ICDs. Both hVISA and MRSA are associated with high mortality. Low rates of surgical intervention and P/ICD extraction reflect the high co-morbidity of patients. Caution should be employed in the empirical use of daptomycin in hVISA patients., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Background: The study objective was to define the risk factors and the route of Staphylococcus aureus transmission between mother and newborn., Methods: Women at late pregnancy were screened for nasal and vaginal S. aureus colonization. Newborns were screened for nasal, auricular, umbilical, and rectal colonization at birth and before discharge. Carrier mothers and their newborns were rescreened at 1 month. Pulse-field gel electrophoresis was used to assess strain genetic relatedness., Results: Of the 208 women screened, 34% were colonized with S. aureus. Overall, by 72-100 hours after birth, the cumulative incidence of S. aureus acquisition was 42.6/100 newborns of carrier mothers versus 7.4/100 newborns of noncarrier mothers (adjusted risk ratio = 5.7; 95% confidence interval [CI], 2.3-13.9). The risk to acquire a maternal strain was significantly higher than nonmaternal strain (adjusted risk ratio = 1.5; 95% CI, 1.3-1.9); Newborns to carrier mothers were also at a risk to acquire nonmaternal S. aureus strains compared with newborns to noncarrier mothers (adjusted risk ratio = 2.9; 95% CI, 1.6-5.4). The cumulative incidence of S. aureus acquisition was similar among newborns delivered by cesarean versus vaginal delivery (24.5 vs. 23.0/100 cases). At 1-month follow-up, the cumulative incidence of S. aureus acquisition reached 69.7/100 newborns of carrier mothers.Genetically identical strains were isolated in 32/40 (80%) mother-newborn pairs, among these, the source of the newborn strain was a maternal nasal strain in 29/32 (90%)., Conclusions: Newborns of carrier mothers are at risk to acquire S. aureus colonization. Most newborns of carrier mothers are colonized within the first month of life. Horizontal transmission from the mother is probably the major source for S. aureus carriage in newborns.

Background: Staphylococcus aureus colonization typically precedes infection but risk factors for colonization in children are not well defined. Our previous study suggested that S. aureus carriage in children is associated with parental carriage. Here we wished to distinguish the different components that play a role in the risk to a child of a S. aureus-carrying parent., Methods: Between 2002 and 2005, children (0-40 months) and their parents were screened for carriage of S. aureus and Streptococcus pneumoniae during 1 of 6 surveys. Data were collected from the parents and the medical files. Multivariate analysis of possible associated factors and effect modifiers was carried out. Pulse-field gel electrophoresis was performed to determine strain relatedness., Results: A total of 4648 children were screened. S. aureus was isolated from 342 (7.6%) children and 992 (22%) parents. Pairs of parent-child carriers were found in 155 cases, over twice the rate expected by chance (1.66%, P<0.0001). The variable that was most significantly associated with carriage in children was having a parent carrier (OR: 3.35; 95% CI: 2.59-4.33), whereas close contact with peers (as assessed by day care centers attendance or having young siblings) was not associated with carriage. Children<3 months had the highest carriage rate and children aged 6 to 12 months had the lowest (25.4% and 4.3%, respectively, P<0.0001). Breast-feeding was not associated with higher or lower carriage. In 30 of 150 strains studied, >70% parent-child strains were genetically identical., Conclusions: Parental S. aureus colonization, but not DCC attendance or having young siblings, is an independent predictor for staphylococcal carriage in young children.

Background: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) bacteremia is an emerging infection. Our objective was to determine the molecular features of hVISA strains isolated from bacteremic patients and to compare them to methicillin resistant S. aureus (MRSA) and methicillin sensitive S. aureus (MSSA) blood isolates., Results: We assessed phenotypic and genomic changes of hVISA (n = 24), MRSA (n = 16) and MSSA (n = 17) isolates by PCR to determine staphylococcal chromosomal cassette (SCCmec) types, Panton-Valentine leukocidin (PVL) and the accessory gene regulator (agr) loci. Biofilm formation was quantified. Genetic relatedness was assessed by PFGE. PFGE analysis of isolates was diverse suggesting multiple sources of infection. 50% of hVISA isolates carried SCCmec type I, 21% type II; 25% type V; in 4% the SCCmec type could not be identified. Among MRSA isolates, 44% were SCCmec type I, 12.5% type II, 25% type V, 12.5% were non-typable, and 6% were SCCmec type IVd. Only one hVISA isolate and two MSSA isolates carried the PVL. Biofilm formation and agr patterns were diverse., Conclusion: hVISA isolates were diverse in all parameters tested. A considerable number of hVISA and MRSA strains carried the SCCmec type V cassette, which was not related to community acquisition.

Infections with S. aureus with heterogeneous intermediate resistance to vancomycin (hVISA) are occurring more frequently. The detection of these infections, their prevalence, clinical characteristics, and significance are controversial. During 2003 and 2004, all blood culture isolates of methicillin-resistant Staphylococcus aureus (264 patients) at the Sheba Medical Center, Tel Hashomer, Israel, were assessed for hVISA by using the Etest macromethod. A total of 16 patients (6%) were positive for hVISA. Resistance to teicoplanin alone and to vancomycin alone using the Etest macromethod was found in 14 and 10 patients, respectively. Standard MICs to vancomycin were between 1 to 4 mg/ml. Most of these isolates (12 of 16 [75%]) would have been missed without specific testing. The median number of bacteremic days was 4. Seven patients had positive blood cultures for more than 5 days. Twelve patients died, and for eight of these the deaths were directly related to hVISA sepsis. We found that hVISA bacteremia was prevalent in our institution, and we suggest seeking hVISA in patients with persistent S. aureus bacteremia.

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.

Context: Widespread pneumococcal conjugate vaccination may bring about epidemiologic changes in upper respiratory tract flora of children. Of particular significance may be an interaction between Streptococcus pneumoniae and Staphylococcus aureus, in view of the recent emergence of community-acquired methicillin-resistant S aureus., Objective: To examine the prevalence and risk factors of carriage of S pneumoniae and S aureus in the prevaccination era in young children., Design, Setting, and Patients: Cross-sectional surveillance study of nasopharyngeal carriage of S pneumoniae and nasal carriage of S aureus by 790 children aged 40 months or younger seen at primary care clinics in central Israel during February 2002., Main Outcome Measures: Carriage rates of S pneumoniae (by serotype) and S aureus; risk factors associated with carriage of each pathogen., Results: Among 790 children screened, 43% carried S pneumoniae and 10% carried S aureus. Staphylococcus aureus carriage among S pneumoniae carriers was 6.5% vs 12.9% in S pneumoniae noncarriers. Streptococcus pneumoniae carriage among S aureus carriers was 27.5% vs 44.8% in S aureus noncarriers. Only 2.8% carried both pathogens concomitantly vs 4.3% expected dual carriage (P =.03). Risk factors for S pneumoniae carriage (attending day care, having young siblings, and age older than 3 months) were negatively associated with S aureus carriage., Conclusions: Streptococcus pneumoniae carriage, specifically of vaccine-type strains, is negatively associated with S aureus carriage in children. The implications of these findings in the pneumococcal vaccine era require further investigation.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasingly documented worldwide. We recently identified two major CA-MRSA clones in Israel: USA300 and t991. Here, we assessed clinical outcomes by CA-MRSA clones and the physicians' treatment approach to CA-MRSA infections. All community-onset, clinical MRSA isolates detected during 2011-2013 by Maccabi Healthcare Services were collected and characterized phenotypically and genotypically; data were collected retrospectively from electronic medical records. Of 309 patients with MRSA infections, 64 were identified as CA-MRSA (21 %). Of the CA-MRSA infections, 72 % had skin and soft tissue infections (SSTIs), 38 % were Panton-Valentine leukocidin (PVL)+, the major clone being USA300 ( n = 13, 54 %). Of PVL− isolates ( n = 40, 62 %), t991 was the major clone. Age was the only predictor for PVL+ CA-MRSA infection ( p < 0.001). Patients with PVL+ CA-MRSA had higher incidence of SSTI recurrences (1.061 vs. 0.647 events per patient/per year, p < 0.0001) and were more likely to have the SSTI drained (64 % vs. 21 %, p = 0.003) when compared to PVL− CA-MRSA. USA300 was more common among adults, while t991 was more common among children ( p = 0.002). The physician's referral to culture results and susceptibility were the only predictors of appropriate antibiotic therapy ( p < 0.001). However, only a minority of physicians referred to culture results, regardless of subspecialties. PVL+ CA-MRSA isolates caused significantly more recurrences of SSTIs and increased the need for drainage compared with PVL− isolates. Physicians' awareness of CA-MRSA as a cause of SSTIs in the community was suboptimal. Culturing of pus-producing SSTIs is crucial for providing adequate antimicrobials and elucidating MRSA epidemiology. [ABSTRACT FROM AUTHOR]