Functional dynamics of Foxp3⁺ regulatory T cells in mice and humans.

Forkhead box protein 3 (Foxp3)(+) regulatory T (Treg) cells are critical mediators for the establishment of self-tolerance and immune homeostasis and for the control of pathology in various inflammatory responses. While Foxp3(+) Treg cells often control immune responses in secondary lymphoid tissues, they must also traffic to and persist within non-lymphoid tissues, where they integrate various environmental cues to coordinate and adapt their effector acitvities in these sites. In recent years, our group has made use of several mouse models, including the non-obese diabetic model of type 1 diabetes, to characterize the factors, which impact the homeostasis, function, and reprogramming potential of Foxp3(+) Treg cells in situ. In addition, our recent work shows that Foxp3(+) Treg cells possess distinct post-transcriptional mechanisms of gene regulation, namely mRNA translation, to modulate tissue-specific inflammatory responses. In humans, there is a pressing need for reliable markers of FOXP3(+) Treg cells and their related function in blood and tissue. Experimental progress in our group has enabled us to discover novel markers of FOXP3(+) Treg cell (dys)function and unique gene signatures that discriminate effector and Treg cells, as well as functional and dysfunctional FOXP3(+) Treg cells.

Pneumococcal Pneumonia Requiring Hospitalization in US Children in the 13-Valent Pneumococcal Conjugate Vaccine Era.

BACKGROUND.: The impact of PCV13 on a number of clinical aspects of pneumococcal pneumonia (PP) in children has not been reported. We compared the serotype distribution, antibiotic susceptibility, and outcomes of children with PP 4 years before and 4 years after the introduction of PCV13. METHODS.: We identified patients ≤18 years with PP at 8 children's hospitals in the United States (2006-2014). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical and laboratory data were collected retrospectively. Annual pneumococcal pneumonia hospitalization rates per 100 000 admissions with 95% confidence intervals were calculated. Dichotomous variables were analyzed by χ2 test and continuous variables with Mann-Whitney U test. RESULTS.: A total of 377 patients with PP requiring hospitalization were identified. Hospitalization rates of PP decreased from 53.6 to 23.3 per 100000 admissions post PCV13 (P < .0001). Complicated PP rates also decreased (P < .0001). Need for intensive care, mechanical ventilation, and invasive procedure remained unchanged after the introduction of PCV13. Comorbidities were more common among children with uncomplicated than complicated pneumonia (52.2% vs. 22.5%, P < .001). Overall, PCV13 serotypes 19A, 3, 7F, and 1 caused 80% of PP. Hospitalization rates of PCV13 serotype pneumonia decreased from 47.2 to 15.7 per 100000 admissions post PCV13. In 2014, the most common serotypes were 3, 19A and 35B. CONCLUSIONS.: PP requiring hospitalization significantly decreased in children after PCV13 introduction. Complicated PP rates decreased steadily in 2011-2014. PCV13 serotypes 19A and 3 were still responsible for half of the cases of PP in 2011-2014.

Impact of Health Care Exposure on Genotypic Antiseptic Tolerance in Staphylococcus aureus Infections in a Pediatric Population.

Staphylococcus aureus possessing either the smr gene or the qacA/B genes is associated with decreased susceptibility to chlorhexidine gluconate (CHG) and other antiseptics. Previous studies of antiseptic-tolerant staphylococci have focused largely on high-risk populations, and the exact role of health care exposure in the acquisition of these organisms is unclear. We sought to describe the risk factors and features of infection caused by antiseptic-tolerant S. aureus in a general pediatric population. Isolates were selected from an ongoing S. aureus surveillance study. Every third sequential isolate in the year 2014 was selected for inclusion. All isolates underwent PCR for the genes qacA/B and smr Medical records were reviewed. Five hundred six isolates were included in the study, with 377 (74.3%) being community acquired. One hundred (19.8%) isolates were smr positive and 79 (15.6%) qacA/B positive. In univariable analyses, the presence of either gene was associated with underlying medical conditions, nosocomial acquisition, recent hospitalization, central venous lines, and CHG exposure. In multivariable analyses, only differences between patients with chronic medical conditions (odds ratio [OR] = 1.72; 95% confidence interval [CI], 1.22 to 2.64) and nosocomial acquisition (OR = 2.48; 95% CI, 1.16 to 8.17) remained statistically significant. Among patients without risk factors, 27.9% had infection with an antiseptic-tolerant isolate. smr- or qacA/B-positive S. aureus isolates are common in children and are independently associated with nosocomial acquisition and underlying medical conditions. These findings imply a role for the health care environment in acquisition of these organisms. However, genotypic antiseptic tolerance was seen in >25% of healthy children with an S. aureus infection, indicating that these organism are prevalent in the community as well.

Emergence of Multidrug-Resistant Pneumococcal Serotype 35B among Children in the United States.

Streptococcus pneumoniae serotype 35B is a nonvaccine serotype associated with high rates of penicillin nonsusceptibility. An increase in the proportion of multidrug-resistant (MDR) 35B isolates has recently been reported. The genetic events contributing to the emergence of MDR serotype 35B are unknown. The sequence type (ST) composition of 78 serotype 35B isolates obtained from pediatric patients with invasive pneumococcal disease from 1994 to 2014 and 48 isolates from pediatric patients with otitis media (noninvasive) from 2011 to 2014 was characterized by multilocus sequence typing (MLST). The most common STs were ST558 (69.2%), ST156 (10.3%), and ST452 (3.8%). Two major clonal complexes (CC), CC558 and CC156, were identified by eBURST analysis. Overall, 91% (71/78) of isolates were penicillin nonsusceptible and 16.7% (13/78) were MDR. Among all invasive serotype 35B isolates, MDR isolates increased significantly, from 2.9% (1/35) to 27.9% (12/43) (P = 0.004), after the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced. All CC156 isolates were identified after the introduction of PCV13 (0/35 [0%] before versus 9/43 [20.9%] after; P = 0.003) and were MDR. All CC156 isolates had similar antimicrobial susceptibility patterns; in contrast, high variability in antimicrobial susceptibility was observed among CC558 isolates. The distributions of CC558 and CC156 among invasive and noninvasive isolates were not different. The increased prevalence of MDR serotype 35B after the introduction of PCV13 was directly associated with the emergence of ST156. Genotyping suggests that capsular switching has occurred between MDR vaccine serotypes belonging to ST156 (e.g., 9V, 14, and 19A) and serotype 35B.

Invasive pneumococcal infections in children following transplantation in the pneumococcal conjugate vaccine era.

BACKGROUND: Pediatric recipients of hematopoietic stem cell and solid organ transplants are at increased risk of invasive pneumococcal infections (IPI). Data on IPI in this population are scarce. To our knowledge, this is the first study describing the epidemiology of IPI among pediatric transplant recipients in the pneumococcal conjugate vaccine (PCV) era. METHODS: We identified transplant recipients with IPI at 8 children's hospitals in the U.S. from our surveillance database (2000-2014). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Categorical variables were analyzed by Fisher's exact test and continuous variables with nonparametric tests. Indirect cohort study design was used to calculate vaccine effectiveness. RESULTS: We identified 65 episodes of IPI in transplant recipients. Recurrent IPI was observed in 10% of transplant recipients. The IPI crude incidence rate in solid organ transplant recipients was higher than in the general population. Most IPI episodes occurred >6 months after transplantation. Bacteremia and pneumonia were the most common presentations. Meningitis was unusual. No case fatalities were observed. Serotype 19A was the most common serotype (n=10), followed by 6C (n=7). In 2010-2014, 37% of IPI was caused by PCV13 serotypes. Four cases of vaccine breakthrough were identified. Most isolates were susceptible to penicillin and ceftriaxone. Pneumococcal conjugate and polysaccharide immunization rates were low. CONCLUSION: Pediatric transplant recipients remain at increased risk of IPI in the vaccine era. Most cases presented as a late post-transplant infection. The interval between transplantation and IPI may allow adequate time for pneumococcal immunization.

Clinical and Epidemiological Evidence of the Red Queen Hypothesis in Pneumococcal Serotype Dynamics.

BACKGROUND: The Red Queen hypothesis is an evolutionary theory that describes the reciprocal coevolution of competing species. We sought to study whether introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) altered pneumococcal serotype dynamics among children with invasive pneumococcal disease (IPD) as predicted by the Red Queen hypothesis. METHODS: This study examined pneumococcal isolates (n = 641) obtained from children <18 years of age hospitalized with IPD from 1997 to 2014 in Utah. A review of the literature also identified several additional studies conducted in the United States and Europe that were used to test the external generalizability of our Utah findings. Simpson's index was used to quantify pneumococcal serotype diversity. RESULTS: In Utah, the introduction of PCV7 and PCV13 was associated with rapid increases in serotype diversity (P < .001). Serotypes rarely present before vaccine introduction emerged as common causes of IPD. Diversity then decreased (P < .001) as competition selected for the fittest serotypes and new evolutionary equilibriums were established. This pattern was also observed more broadly in the United States, the United Kingdom, Norway, and Spain. CONCLUSIONS: This vaccine-driven example of human/bacterial coevolution appears to confirm the Red Queen hypothesis, which reveals a limitation of serotype-specific vaccines and offers insights that may facilitate alternative strategies for the elimination of IPD.

Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital.

One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial Staphylococcus aureus isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an S. aureus surveillance study at Texas Children's Hospital. Nosocomial S. aureus isolates (those causing infection at ≥72 h of hospitalization) were identified and underwent PCR for the qacA or qacB (qacA/B) and smr genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and agr typing and a review of the medical record were performed. Two hundred forty-seven nosocomial S. aureus infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for smr, 22.7% were positive for qacA/B, and 10.9% of the isolates possessed both genes. The smr-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for qacA/B were more often associated with indwelling central venous catheters and a vancomycin MIC of ≥2 µg/ml. Isolates carrying either smr or qacA/B were associated with a diagnosis of bacteremia. The smr-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for qacA/B. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptic-tolerant S. aureus strains are common in our children's hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children.

BACKGROUND: The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13. METHODS: We identified patients ≤ 18 years of age with PM at 8 children's hospitals in the United States. Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical data were abstracted from medical records. Patients were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010), and post-PCV13 (2011-2013). Categorical variables were analyzed by the χ(2) test and continuous variables by the Mann--Whitney U test. RESULTS: During the study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%) during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13 serotype cases represented 73% of the isolates in 2011-2013. Isolates with ceftriaxone minimum inhibitory concentration ≥ 1 µg/mL decreased (13% to 3%) from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified for hospital course or outcome, with the exception that a greater proportion of patients had subdural empyema and hemiparesis in 2011-2013. CONCLUSIONS: After the introduction of PCV13, the number of cases of PM in children remained unchanged compared with 2007-2009, although the proportion of PCV13 serotypes decreased significantly. Serotype 19A continued to be the most common serotype in 2011-2013. Antibiotic resistance decreased significantly. Morbidity and case-fatality rate due to PM remain substantial.

Multicenter surveillance of Streptococcus pneumoniae isolates from middle ear and mastoid cultures in the 13-valent pneumococcal conjugate vaccine era.

BACKGROUND: Streptococcus pneumoniae is a common cause of otitis media (OM) in children; mastoiditis remains an important complication of OM. Limited data are available on the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal otitis. METHODS: Investigators from 8 children's hospitals in the United States prospectively collected pneumococcal isolates from middle ear or mastoid cultures from children from 2011 to 2013. Serotype and antibiotic susceptibilities were determined and PCV13 doses for children documented. RESULTS: Over the 3-year period, the proportion of isolates included in PCV13 (plus a related serotype) decreased significantly (P = .0006) among the middle ear/mastoid isolates (2011, 50% [74/149]; 2012, 40.5% [47/116]; 2013, 29% [34/118]). The number of serotype 19A isolates in 2013 (n = 12, 10.2% of total) decreased 76% compared with the number of 19A isolates in 2011 (n = 50, 33.6% of total). Of the children from whom serotype 19A was isolated (n = 93), 55% had previously received <3 doses of PCV13. The most common non-PCV13 serotypes for the combined years were 35B (n = 37), 21 (n = 20), 23B (n = 20), 15B (n = 18), 11 (n = 17), 23A (n = 14), 15A (n = 14), and 15C (n = 14). The proportion of isolates with a penicillin minimal inhibitory concentration >2 µg/mL decreased significantly over the 3 years (2011, 22% [35/154]; 2012, 20% [24/118]; 2013, 10% [12/120]; P < .02). CONCLUSIONS: The number of pneumococcal isolates and the percentage of isolates with high-level penicillin resistance from cultures taken from children with OM or mastoiditis for clinical indications have decreased following PCV13 use, largely related to decreases in serotype 19A isolates.

Characterization of Staphylococcus aureus infections in children with Down syndrome.

Staphylococcus aureus infections in the Down syndrome (DS) population have not been well characterized. This study determined clinical and molecular characteristics of S. aureus infections in children with DS followed at Texas Children's Hospital (TCH), from 2001 to 2011. Patients were retrospectively identified from an ongoing S. aureus surveillance study. Medical records were reviewed. Isolates were characterized by antimicrobial susceptibility, pulsed-field gel electrophoresis patterns, and detection of PVL genes (pvl), mupA (high-level mupirocin resistance gene), smr (chlorhexidine resistance conferring gene), and Staphylococcal Chromosomal Cassette mec (SCCmec) type. Twenty-six patients with DS had a total of 34 S. aureus infections (8 recurrent); 61% were MRSA. DS patients represented 16.8 per 10,000 community onset S. aureus infections seen at TCH. Among 26 initial infections 17 were skin and soft tissue (SSTI), 7 were outer or middle ear and 2 were invasive infections. Seventeen patients were hospitalized. Thirteen (65%) of 20 available isolates were USA300, 14 were pvl+, 5 were mupA+, and 8 were smr+. Five of 8 (63%) recurrent infections were ear infections. All 4 recurrent ear isolates available for study were smr+, ciprofloxacin non-susceptible and treated with ciprofloxacin otic drops. S. aureus infections among patients with DS were similar in presentation to other patient groups, except for a greater proportion being associated with ear infections. Seventy percent of ear fluid isolates carried antiseptic and fluoroquinolone resistance genes. A study of a greater number of DS patients is warranted to further explore these findings.

Randomized trial of "bleach baths" plus routine hygienic measures vs. routine hygienic measures alone for prevention of recurrent infections.

Children with probable community-associated Staphylococcus aureus skin and soft tissue or invasive infections were randomized to routine daily hygienic measures with or without "bleach baths" twice a week for 3 months. Within 12 months, a medically attended recurrence occurred in 84 of 495 (17%) children using bleach baths compared to 103 of 492 (21%) of control participants (P = .15).

Decreased susceptibilities to Retapamulin, Mupirocin, and Chlorhexidine among Staphylococcus aureus isolates causing skin and soft tissue infections in otherwise healthy children.

Topical antimicrobial and antiseptic agents are commonly used in the management of minor skin and soft tissue infections (SSTIs). Resistance to mupirocin has been documented in Staphylococcus aureus isolates causing SSTIs. Data are limited, however, on the prevalence of retapamulin resistance or tolerance to antiseptics. We sought to determine the prevalence of decreased susceptibility to retapamulin and mupirocin as well as the potential for decreased chlorhexidine susceptibility of S. aureus isolates from SSTIs in children. Two hundred isolates from patients with a single SSTI and 200 isolates from patients with ≥3 previous episodes from the years 2010 to 2012 were selected from an S. aureus surveillance study. Screening for retapamulin resistance was performed by the broth macrodilution method; mupirocin MICs were determined by Etest. PCR was performed for the presence of the smr gene associated with elevated MICs/minimum bactericidal concentrations (MBCs) to chlorhexidine. Among the isolates screened, 38 isolates (9.5%) exhibited retapamulin resistance, of which 22 (57.9%) were methicillin-resistant S. aureus (MRSA). Two isolates (0.5%) displayed cross-resistance to retapamulin and linezolid. Thirty-nine isolates (9.8%) were found to have mupirocin resistance. smr-positive S. aureus accounted for 14% of isolates. The proportion of smr-positive organisms increased during the study (P = 0.005). The prevalence of in vitro resistance to topical antimicrobials among S. aureus isolates causing SSTI in healthy children in our community is almost 10%. Retapamulin resistance was associated with cross-resistance to linezolid in 0.5% of isolates. In addition, there was an increase in the proportion of smr-positive isolates. Further research including clinical correlations with these findings is warranted.

A fluvial mercury budget for Lake Ontario.

Watershed mercury (Hg) flux was calculated for ten inflowing rivers and the outlet for Lake Ontario using empirical measurements from two independent field-sampling programs. Total Hg (THg) flux for nine study watersheds that directly drain into the lake ranged from 0.2 kg/yr to 13 kg/yr, with the dominant fluvial THg load from the Niagara River at 154 kg/yr. THg loss at the outlet (St. Lawrence River) was 68 kg/yr and has declined approximately 40% over the past decade. Fluvial Hg inputs largely (62%) occur in the dissolved fraction and are similar to estimates of atmospheric Hg inputs. Fluvial mass balances suggest strong in-lake retention of particulate Hg inputs (99%), compared to dissolved total Hg (45%) and methyl Hg (22%) fractions. Wetland land cover is a good predictor of methyl Hg yield for Lake Ontario watersheds. Sediment deposition studies, coupled atmospheric and fluvial Hg fluxes, and a comparison of this work with previous measurements indicate that Lake Ontario is a net sink of Hg inputs and not at steady state likely because of recent decreases in point source inputs and atmospheric Hg deposition.

Changes in Streptococcus pneumoniae serotype 19A invasive infections in children from 1993 to 2011.

Among 594 Streptococcus pneumoniae serotype 19A invasive pneumococcal disease (IPD) isolates collected from 1993 to 2011, we identified 85 sequence types by multilocus sequence typing. CC320 was associated with multidrug resistance and reduced susceptibility to penicillin and ceftriaxone and still predominated among declining serotype 19A IPD isolates following PCV13 introduction.

Characterization of nontypeable and atypical Streptococcus pneumoniae pediatric isolates from 1994 to 2010.

Streptococcus pneumoniae is a major cause of bacteremia, meningitis, pneumonia, sinusitis, and acute otitis media in children. Although optochin susceptibility, bile solubility, and Quellung testing are the standards for identifying and differentiating pneumococci, there are several reports of nontypeable pneumococci that give inconsistent results with one or more of these tests. We characterized 52 isolates previously labeled as nontypeable pneumococci. Microbiological methods included repeating the Quellung reaction using a new and expanded group of antisera, optochin susceptibility and bile solubility tests, and automated Vitek 2 identification. Molecular methods included PCR detection of ply and psaA genes, multilocus sequence typing (MLST), 16S rRNA gene sequencing, and pyrosequencing. Of the 52 isolates, 38 (73%) were optochin susceptible, were psaA and ply positive, and could be serotyped by the Quellung reaction. The remaining 14 isolates, isolated from patients with otitis media (n = 6), bacteremia (n = 6), meningitis (n = 1), and pneumonia (n = 1), underwent further analysis. Three of these 14 isolates were nontypeable due to autoagglutination but were pneumococci by all tests and represented pneumococcal sequence types previously recognized by MLST. The 11 remaining isolates were optochin resistant, and 6 of these were bile soluble. Three of 11 were both psaA and ply positive and clustered with pneumococci by MLST (2 were bile soluble); 8 lacked psaA (5 ply positive, 4 bile soluble) and likely belonged to other Streptococcus species. In conclusion, few isolates were truly nontypeable by Quellung reaction, and MLST and the presence of psaA proved useful in distinguishing between atypical pneumococci and other streptococcal species.

Community-acquired staphylococcal musculoskeletal infection in infants and young children: necessity of contrast-enhanced MRI for the diagnosis of growth cartilage involvement.

OBJECTIVE: Previous studies have reported that contrast-enhanced sequences do not increase the sensitivity of MRI for the diagnosis of pediatric osteomyelitis and are not needed in the absence of edema on unenhanced MRI sequences. Invasive skeletal infections due to community-acquired Staphylococcus aureus are increasingly encountered in infants and young children and have a proclivity for involvement of both the unossified growth cartilage and the metadiaphyseal bone marrow of the extremities. The study objective is to assess the diagnostic efficacy of contrast-enhanced and unenhanced MRI sequences for the diagnosis of community-acquired S. aureus extremity skeletal infection in infants and young children. MATERIALS AND METHODS: A retrospective review was conducted of the clinical charts and imaging studies of patients younger than 18 months diagnosed with invasive community-acquired S. aureus skeletal infections from 2001 to 2009 at a large children's hospital. Sensitivity was calculated for the detection of skeletal infection on contrast-enhanced and unenhanced MRI sequences. The p values were calculated using the Fisher exact score method. The kappa value for interobserver reliability was determined. RESULTS: Community-acquired S. aureus skeletal infections were noted in 34 extremity sites in 25 patients, five of whom had more than one site of disease. The affected skeletal sites were metaphyseal or metadiaphyseal bone marrow only in 16 cases (47%), unossified growth cartilage only in nine cases (26%), and both the unossified growth cartilage and metaphyseal or metadiaphyseal bone marrow in nine cases (26%). In seven of the nine cases of isolated involvement of the unossified growth cartilage, the cartilage appeared normal on unenhanced sequences and the diagnosis was made only by the demonstration of hypoenhancing or nonenhancing foci in the cartilage after gadolinium-based contrast agent administration. In five of the nine cases of infection of both the unossified growth cartilage and metaphyseal or metadiaphyseal bone marrow, neither the cartilage nor bone marrow appeared abnormal on unenhanced sequences. Therefore, 12 cases of skeletal infection would have been missed without the inclusion of contrast-enhanced sequences. Follow-up extremity radiographs were available for 10 patients, eight (80%) of whom exhibited growth disturbances. CONCLUSION: Skeletal infection caused by community-acquired S. aureus in infants and young children manifests differently than in older children, including a propensity for involvement of the unossified growth cartilage and potentially occult nature of both cartilage and bone marrow involvement on unenhanced MRI sequences.

Mupirocin resistance in Staphylococcus aureus causing recurrent skin and soft tissue infections in children.

Staphylococcus aureus resistance to mupirocin is often caused by acquisition of a novel isoleucyl-tRNA synthetase encoded on the plasmid gene mupA. We tested S. aureus isolates from children at Texas Children's Hospital with recurrent skin and soft tissue infections for mupirocin resistance and mupA. Of 136 isolates, 20 were resistant to mupirocin (14.7%). Fifteen isolates (11%) carried mupA, and the gene was more common in methicillin-susceptible S. aureus (21.4%) than methicillin-resistant S. aureus (8.3%; P=0.03). Seven of 20 mupirocin-resistant isolates displayed clindamycin resistance.

Increase in prevalence of Streptococcus pneumoniae serotype 6C at Eight Children's Hospitals in the United States from 1993 to 2009.

Streptococcus pneumoniae serotype 6C, which was described in 2007, causes invasive disease in adults and children. We investigated the prevalence of 6C among pediatric isolates obtained from eight children's hospitals in the United States. S. pneumoniae isolates were identified from a prospective multicenter study (1993 to 2009). Fifty-seven serotype 6C isolates were identified by multiplex PCR and/or Quellung reaction. Five were isolated before 2000, and the prevalence increased over time (P < 0.000001). The median patient age was 2.1 years (range, 0.2 to 22.5 years). Clinical presentations included bacteremia (n = 24), meningitis (n = 7), pneumonia (n = 4), abscess/wound (n = 3), mastoiditis (n = 2), cellulitis (n = 2), peritonitis (n = 1), septic arthritis (n = 1), otitis media (n = 10), and sinusitis (n = 3). By broth microdilution, 43/44 invasive serotype 6C isolates were susceptible to penicillin (median MIC, 0.015 µg/ml; range, 0.008 to 2 µg/ml); all were susceptible to ceftriaxone (median MIC, 0.015 µg/ml; range, 0.008 to 1 µg/ml). By disk diffusion, 16/44 invasive isolates (36%) were nonsusceptible to erythromycin, 19 isolates (43%) were nonsusceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and all isolates were clindamycin susceptible. Multilocus sequence typing (MLST) revealed 24 sequence types (STs); 9 were new to the MLST database. The two main clonal clusters (CCs) were ST473 and single-locus variants (SLVs) (n = 13) and ST1292 and SLVs (n = 23). ST1292 and SLVs had decreased antibiotic susceptibility. Serotype 6C causes disease in children in the United States. Emerging CC1292 expressed TMP-SMX resistance and decreased susceptibility to penicillin and ceftriaxone. Continued surveillance is needed to monitor changes in serotype prevalence and possible emergence of antibiotic resistance in pediatric pneumococcal disease.

Molecular epidemiology of pediatric pneumococcal empyema from 2001 to 2007 in Utah.

Utah had a high rate of pediatric pneumococcal empyema (PPE) prior to licensure of the pneumococcal conjugate vaccine (PCV-7) in 2000. The majority (62%) of PPE cases was due to nonvaccine serotypes, primarily Streptococcus pneumoniae serotype 1, multilocus sequence type (MLST) 227. PPE in Utah children has increased over the last decade. It is unclear whether the increase was due to serotype replacement or switch. In this study, we describe the incidence and molecular epidemiology of PPE by MLST in Utah children after the licensure of PCV-7. Empyema rates increased from 8.5/100,000 children in the state of Utah in 2001 to 12.5/100,000 children in 2007 (P = 0.006). Ninety-eight percent was due to nonvaccine serotypes (P < 0.001 when compared to the pre-PCV-7 period). PPE was primarily due to serotypes 1, 3, 19A, and 7F, with MLST demonstrating sequence types (ST) that were commonly present in the United States prior to licensure of PCV-7. Serotype switch was not documented. Replacement disease with common ST of serotypes 1,3, 7F, and 19A rather than serotype switch was responsible for the increase in PPE in Utah children.