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Article: Rapid Changes in Nasopharyngeal Antibiotic Resistance Gene Profiles After Short Courses of Antibiotics in a Pilot Study of Ambulatory Young Children.

Howard, Leigh M / Dantuluri, Keerti L / Soper, Nicole / Thomsen, Isaac P / Grijalva, Carlos G

2021 Volume 8, Issue 11, Page(s) ofab519

Abstract: We quantified antibiotic resistance genes before and after short antibiotic courses in nasopharyngeal specimens from ambulatory children. Carriage of certain bacteria and resistance genes was common before antibiotics. After antibiotics, we observed ... ...

Abstract	We quantified antibiotic resistance genes before and after short antibiotic courses in nasopharyngeal specimens from ambulatory children. Carriage of certain bacteria and resistance genes was common before antibiotics. After antibiotics, we observed substantial reductions in pneumococcal and
Language	English
Publishing date	2021-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofab519
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Article ; Online: Association between nasopharyngeal colonization with multiple pneumococcal serotypes and total pneumococcal colonization density in young Peruvian children.

Howard, Leigh M / Huang, Xiang / Chen, Wencong / Liu, Yuhan / Edwards, Kathryn M / Griffin, Marie R / Zhu, Yuwei / Vidal, Jorge E / Klugman, Keith P / Gil, Ana I / Soper, Nicole R / Thomsen, Isaac P / Gould, Katherine / Hinds, Jason / Lanata, Claudio F / Grijalva, Carlos G

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2023 Volume 134, Page(s) 248–255

Abstract: Objectives: We examined the association of nasopharyngeal (NP) pneumococcal co-colonization (>1 pneumococcal serotype) and pneumococcal density in young Peruvian children enrolled in a prospective cohort study.: Methods: NP swabs collected monthly ... ...

Abstract	Objectives: We examined the association of nasopharyngeal (NP) pneumococcal co-colonization (>1 pneumococcal serotype) and pneumococcal density in young Peruvian children enrolled in a prospective cohort study. Methods: NP swabs collected monthly from children aged <3 years during both asymptomatic and acute respiratory illness (ARI) periods underwent culture-enriched microarray for pneumococcal detection and serotyping and lytA polymerase chain reaction for density assessment. We examined the serotypes commonly associated with co-colonization and the distribution of densities by co-colonization, age, current ARI, and other covariates. The association of co-colonization and pneumococcal density was assessed using a multivariable mixed-effects linear regression model, accounting for repeated measures and relevant covariates. Results: A total of 27 children contributed 575 monthly NP samples. Pneumococcus was detected in 302 of 575 (53%) samples, and co-colonization was detected in 61 of these 302 (20%). The total densities were higher during ARI than non-ARI periods and lowest among the youngest children, increasing with age. In the multivariable analysis, there was no significant association between pneumococcal density and co-colonization (coefficient estimate 0.22, 95% confidence interval 0.11-0.55; reference: single-serotype detections). Serotypes 23B and 19F were detected significantly more frequently as single isolates. Conclusion: Pneumococcal co-colonization was common and not associated with increased pneumococcal density. Differential propensity for co-colonization was observed among individual serotypes.
MeSH term(s)	Humans ; Child ; Infant ; Streptococcus pneumoniae ; Serogroup ; Pneumococcal Infections/epidemiology ; Prospective Studies ; Peru/epidemiology ; Nasopharynx ; Pneumococcal Vaccines ; Carrier State/epidemiology
Chemical Substances	Pneumococcal Vaccines
Language	English
Publishing date	2023-07-13
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2023.07.007
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Article ; Online: Adoptive Transfer of Serum Samples From Children With Invasive Staphylococcal Infection and Protection Against Staphylococcus aureus Sepsis.

Tsai, Chih-Ming / Soper, Nicole / Bennett, Monique / Fallon, Jonathan K / Michell, Ashlin R / Alter, Galit / Liu, George Y / Thomsen, Isaac

The Journal of infectious diseases

2020 Volume 223, Issue 7, Page(s) 1222–1231

Abstract: A successful Staphylococcus aureus vaccine remains elusive, and one controversy in the field is whether humans generate a protective adaptive immune response to infection. We developed a bacterial challenge murine assay that directly assesses the ... ...

Abstract	A successful Staphylococcus aureus vaccine remains elusive, and one controversy in the field is whether humans generate a protective adaptive immune response to infection. We developed a bacterial challenge murine assay that directly assesses the protective capacity of adoptively transferred human serum samples. We first validated the model by showing that postpneumococcal vaccine serum samples from humans induced effective clearance of Streptococcus pneumoniae in mice. We then found that human serum samples adoptively transferred from children with invasive S. aureus infections exhibited protection from disease in a murine model, with some samples conferring near complete protection. These findings demonstrate that human serum samples are capable of conferring a protective adaptive response generated by humans during invasive staphylococcal disease, allowing for the study of protective factors in a murine model. Identification of the protective factors present in the most efficacious serum samples would be of high interest as potential staphylococcal vaccine candidates or passive therapeutics.
MeSH term(s)	Adoptive Transfer ; Animals ; Antibodies, Bacterial/immunology ; Child ; Disease Models, Animal ; Humans ; Mice ; Sepsis/prevention & control ; Staphylococcal Infections/prevention & control ; Staphylococcus aureus
Chemical Substances	Antibodies, Bacterial
Language	English
Publishing date	2020-09-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiaa482
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Article ; Online: Molecular Epidemiology of Invasive Staphylococcus aureus Infections and Concordance with Colonization Isolates.

Thomsen, Isaac P / Kadari, Priyanka / Soper, Nicole R / Riddell, Scott / Kiska, Deanna / Creech, C Buddy / Shaw, Jana

The Journal of pediatrics

2019 Volume 210, Page(s) 173–177

Abstract: Objectives: To characterize Staphylococcus aureus isolates recovered from hospitalized children and to determine the concordance between colonizing and invasive isolates.: Study design: Children with culture-confirmed, community-onset, invasive S ... ...

Abstract	Objectives: To characterize Staphylococcus aureus isolates recovered from hospitalized children and to determine the concordance between colonizing and invasive isolates. Study design: Children with culture-confirmed, community-onset, invasive S aureus infections were enrolled in this prospective case series from a large children's hospital over a 5-year period. Colonization isolates were obtained from the anterior nares, oropharynx, and inguinal folds and were compared with invasive isolates via repetitive-element, sequence-based polymerase chain reaction testing. Isolates with a ≥96% genetic match were characterized as concordant. Results: A total of 86 S aureus isolates (44 invasive, 42 colonization) were collected from 44 children with invasive infections. Clinical isolates were genetically diverse, 64% of invasive isolates were methicillin-susceptible S aureus (MSSA), and 59% of cases had a colonizing S aureus isolate at the time of hospitalization. Of those who were colonized, at least 1 of their colonization isolates was indistinguishable from the infecting isolate in 88% of cases. Patients with invasive MSSA were significantly more likely to have a concordant MSSA colonization isolate present compared with patients with invasive methicillin-resistant S aureus (MRSA) (61% vs 38%, P < .05). Conclusions: Invasive MSSA infection was more common than MRSA infection in this pediatric cohort, and patients with MSSA infection were significantly more likely than those with MRSA infection to have concordant colonizing isolates across multiple anatomic sites. These findings warrant larger scale validation and may have important infection control and epidemiologic implications, as unlike MRSA, transmissibility of MSSA largely is ignored in healthcare settings.
MeSH term(s)	Adolescent ; Carrier State ; Child ; Child, Preschool ; Community-Acquired Infections/epidemiology ; DNA, Bacterial/genetics ; Female ; Groin/microbiology ; Humans ; Infant ; Infant, Newborn ; Male ; Molecular Epidemiology ; Nasal Cavity/microbiology ; New York/epidemiology ; Oropharynx/microbiology ; Polymerase Chain Reaction ; Prospective Studies ; Staphylococcal Infections/epidemiology ; Staphylococcus aureus/genetics ; Staphylococcus aureus/isolation & purification
Chemical Substances	DNA, Bacterial
Language	English
Publishing date	2019-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2019.03.004
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Article ; Online: Serologic Detection of Antibodies Targeting the Leukocidin LukAB Strongly Predicts Staphylococcus aureus in Children With Invasive Infection.

Wood, James B / Jones, Lauren S / Soper, Nicole R / Xu, Meng / Torres, Victor J / Buddy Creech, C / Thomsen, Isaac P

Journal of the Pediatric Infectious Diseases Society

2018 Volume 8, Issue 2, Page(s) 128–135

Abstract: Background: Staphylococcus aureus is among the most commonly identified causes of invasive bacterial infection in children; however, reliable results from cultures of sterile-site samples often cannot be obtained, which necessitates prescription of a ... ...

Abstract	Background: Staphylococcus aureus is among the most commonly identified causes of invasive bacterial infection in children; however, reliable results from cultures of sterile-site samples often cannot be obtained, which necessitates prescription of a broad empiric antimicrobial agent(s). Children with invasive S aureus infection rapidly generate high antibody titers to the cytotoxin LukAB; therefore, the aim of this study was to assess the diagnostic utility of an anti-LukAB antibody assay for children with musculoskeletal infection (MSKI). Methods: We conducted a 2-year prospective study of all eligible children admitted to Vanderbilt Children's Hospital with an MSKI. Acute and convalescent sera were obtained, and antibodies that target LukAB were measured by an enzyme-linked immunosorbent assay. Results: Forty-two children were enrolled. The median concentrations of LukAB antibodies for children with S aureus infection were 130.3 U/mL in the acute phase and 455 U/mL in the convalescent phase (P < .001). The median concentrations of LukAB antibodies in children with a non-S aureus MSKI were 8.6 U/mL in the acute phase and 9.7 U/mL in the convalescent phase. The assay discriminated between S aureus and non-S aureus infection with areas under the receiver operating characteristic curve of 0.81 (95% confidence interval, 0.67-0.95; P < .001) and 0.95 (95% confidence interval, 0.86-1; P < .001) for samples tested in the acute and follow-up periods, respectively. With no false-negative results, the assay accurately ruled out S aureus in samples obtained during the convalescent phase. Conclusion: Culture-independent diagnostics have the potential to improve care by narrowing antimicrobial therapy on the basis of the likelihood of S aureus infection. The results of this proof-of-concept study suggest that a LukAB serologic assay might be useful in the diagnosis of invasive bacterial infections, and larger-scale validation studies are warranted.
MeSH term(s)	Antibodies, Bacterial/blood ; Bacterial Proteins/immunology ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Histocompatibility Antigens Class II ; Hospitals, Pediatric ; Humans ; Immunoglobulin G/blood ; Infant ; Leukocidins/immunology ; Male ; Musculoskeletal Diseases/complications ; Musculoskeletal Diseases/microbiology ; Prospective Studies ; Staphylococcal Infections/diagnosis ; Staphylococcal Infections/immunology ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/immunology ; United States
Chemical Substances	Antibodies, Bacterial ; Bacterial Proteins ; Histocompatibility Antigens Class II ; Immunoglobulin G ; Leukocidins ; leukocidin AB, Staphylococcus aureus
Language	English
Publishing date	2018-03-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piy017
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Article ; Online: Commercial Intravenous Immunoglobulin Preparations Contain Functional Neutralizing Antibodies against the Staphylococcus aureus Leukocidin LukAB (LukGH).

Wood, James B / Jones, Lauren S / Soper, Nicole R / Nagarsheth, Meera / Creech, C Buddy / Thomsen, Isaac P

Antimicrobial agents and chemotherapy

2017 Volume 61, Issue 11

Abstract: The pathogenesis ... ...

Abstract	The pathogenesis of
MeSH term(s)	Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibody Affinity/immunology ; Bacterial Proteins/immunology ; Child ; Child, Preschool ; Humans ; Immunoglobulins, Intravenous/immunology ; Leukocidins/immunology ; Staphylococcal Infections/immunology ; Staphylococcal Infections/pathology ; Staphylococcal Infections/therapy ; Staphylococcus aureus/immunology ; Staphylococcus aureus/pathogenicity ; Virulence Factors/immunology
Chemical Substances	Antibodies, Neutralizing ; Bacterial Proteins ; Immunoglobulins, Intravenous ; Leukocidins ; Virulence Factors ; leukocidin AB, Staphylococcus aureus
Language	English
Publishing date	2017-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00968-17
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Article ; Online: Association Between Contact Sports and Colonization with Staphylococcus aureus in a Prospective Cohort of Collegiate Athletes.

Jiménez-Truque, Natalia / Saye, Elizabeth J / Soper, Nicole / Saville, Benjamin R / Thomsen, Isaac / Edwards, Kathryn M / Creech, C Buddy

Sports medicine (Auckland, N.Z.)

2017 Volume 47, Issue 5, Page(s) 1011–1019

Abstract: Objective: Athletes have a higher risk of infection with Staphylococcus aureus than the general population. Most studies in athletes have included primarily male contact sports participants and have not assessed S. aureus carriage over time. We aimed to ...

Abstract	Objective: Athletes have a higher risk of infection with Staphylococcus aureus than the general population. Most studies in athletes have included primarily male contact sports participants and have not assessed S. aureus carriage over time. We aimed to examine the epidemiology and risk factors of S. aureus carriage in a cohort of male and female collegiate athletes. Study design: We conducted a prospective cohort study of 377 varsity collegiate athletes from August 2008 to April 2010. A baseline questionnaire ascertained risk factors for colonization. Nasal and oropharyngeal swabs were obtained at enrollment and monthly thereafter to detect S. aureus colonization. The primary outcome was S. aureus colonization, both with methicillin-susceptible and methicillin-resistant S. aureus, as defined by bacterial culture and molecular confirmation. Secondary outcomes were time to colonization with S. aureus and carriage profile, defined as non-carrier, intermittent carrier, or persistent carrier. Results: Overall, 224 contact sports and 153 non-contact sports athletes were enrolled. Contact sports athletes had a higher risk of carrying S. aureus over time: They had higher odds of being colonized with MRSA (OR 2.36; 95 % CI 1.13-4.93) and they tended to carry S. aureus for longer periods of time (intermittent carriage OR 3.60; 95 % CI 2.02-6.40; persistent carriage OR 2.39; 95 % CI 1.21-4.72). Athletes engaged in contact sports also acquired S. aureus more quickly (HR 1.61; 95 % CI 1.02-2.55). Conclusions: Staphylococcus aureus carriage was common in contact sports athletes. These findings suggest that efforts to prevent transmission of S. aureus among athletes should be focused on contact sports teams.
Language	English
Publishing date	2017-05
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	605911-9
ISSN	1179-2035 ; 0112-1642
ISSN (online)	1179-2035
ISSN	0112-1642
DOI	10.1007/s40279-016-0618-6
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Article ; Online: Longitudinal Assessment of Colonization With Staphylococcus aureus in Healthy Collegiate Athletes.

Jiménez-Truque, Natalia / Saye, Elizabeth J / Soper, Nicole / Saville, Benjamin R / Thomsen, Isaac / Edwards, Kathryn M / Creech, C Buddy

Journal of the Pediatric Infectious Diseases Society

2016 Volume 5, Issue 2, Page(s) 105–113

Abstract: Background: Staphylococcus aureus is the leading cause of skin and soft tissue infections in the United States, and S. aureus colonization increases the risk of infection. Although athletes have a higher risk of infection with S. aureus than the general ...

Abstract	Background: Staphylococcus aureus is the leading cause of skin and soft tissue infections in the United States, and S. aureus colonization increases the risk of infection. Although athletes have a higher risk of infection with S. aureus than the general population, most studies in athletes have not assessed colonization. Methods: We conducted a prospective cohort study of Vanderbilt University varsity athletes from August 2008 to April 2010. We assessed nasal and oropharyngeal colonization with methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains by obtaining swabs at enrollment and monthly thereafter until the end of the study. The athletes were also monitored for skin and soft tissue infections. Results: We enrolled 377 athletes and trainers (224 in contact sports and 153 in noncontact sports). The total S. aureus colonization prevalence ranged from 34% to 62%, and for MRSA it ranged from 8% to 29%. The colonization rate in the summer was significantly higher than that in the winter (odds ratio for MRSA [ORMRSA], 1.70 [95% confidence interval (CI), 1.23-2.35]; ORMSSA, 1.38 [95% CI, 1.05-1.82]). Of 603 MRSA isolates, 75% carried the staphylococcal cassette chromosome mec (SCCmec) type IV, and 5% carried the genes encoding Panton-Valentine leukocidin. Nine symptomatic S. aureus infections occurred, 7 of which were between July and September. Conclusions: The S. aureus colonization rate is higher than previously reported and fluctuated over time in this prospective cohort of athletes. The higher colonization prevalence during summer might explain the infectious outbreak during the summer months and may represent a key intervention time for preventing S. aureus disease in athletes.
Language	English
Publishing date	2016-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piu108
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Article ; Online: Methicillin-Resistant Staphylococcus aureus in a Trauma Population: Does Decolonization Prevent Infection?

Maxwell, Robert A / Croft, Chasen A / Creech, C Buddy / Thomsen, Isaac / Soper, Nicole / Brown, Laura E / Mejia, Vicente A / Dart, Benjamin W / Barker, Donald E

The American surgeon

2017 Volume 83, Issue 12, Page(s) 1407–1412

Abstract: The purpose of this study was to determine if a decolonization regimen reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections and if colonization isolates are genetically related to subsequent infectious strains. Trauma ... ...

Abstract	The purpose of this study was to determine if a decolonization regimen reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections and if colonization isolates are genetically related to subsequent infectious strains. Trauma patients admitted to the intensive care unit with positive MRSA nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths and mupirocin (MUP) ointment to the nares or soap and water baths and placebo ointment for five days. Nasal swabs performed at the end of treatment and invasive MRSA infections during the remaining hospitalization were compared with the original nasal isolate via polymerase chain reaction for genetic relatedness as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal swabs over a 22-month period ending in 3/2014. After the five day treatment period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%) for soap and water baths and placebo, P = 0.114. No isolates tested positive for the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr. There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap, P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present in the original nasal swab. There was no difference in all-cause Gram-negative or positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467. CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may reduce the incidence of infection. Subsequent invasive MRSA infections are typically caused by the endogenous colonization strain.
MeSH term(s)	Adult ; Aged ; Anti-Infective Agents, Local/therapeutic use ; Bacterial Proteins/genetics ; Baths ; Chlorhexidine/analogs & derivatives ; Chlorhexidine/therapeutic use ; Cross Infection/prevention & control ; Drug Resistance, Bacterial/genetics ; Female ; Humans ; Intensive Care Units ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Methicillin-Resistant Staphylococcus aureus/genetics ; Methicillin-Resistant Staphylococcus aureus/isolation & purification ; Microbial Sensitivity Tests ; Middle Aged ; Mupirocin/therapeutic use ; Nasal Cavity/microbiology ; Polymerase Chain Reaction ; Prospective Studies ; Staphylococcal Infections/prevention & control ; Trauma Centers ; Treatment Outcome
Chemical Substances	Anti-Infective Agents, Local ; Bacterial Proteins ; Mupirocin (D0GX863OA5) ; chlorhexidine gluconate (MOR84MUD8E) ; Chlorhexidine (R4KO0DY52L)
Language	English
Publishing date	2017-12-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	202465-2
ISSN	1555-9823 ; 0003-1348
ISSN (online)	1555-9823
ISSN	0003-1348
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Article ; Online: Frequency of disinfectant resistance genes in pediatric strains of methicillin-resistant Staphylococcus aureus.

Johnson, James G / Saye, Elizabeth J / Jimenez-Truque, Natalia / Soper, Nicole / Thomsen, Isaac / Talbot, Thomas R / Creech, C Buddy

Infection control and hospital epidemiology

2013 Volume 34, Issue 12, Page(s) 1326–1327

MeSH term(s)	Anti-Infective Agents, Local ; Antiporters/genetics ; Bacterial Proteins/genetics ; Chlorhexidine/analogs & derivatives ; DNA, Bacterial/analysis ; Disinfectants ; Drug Resistance, Bacterial/genetics ; Membrane Transport Proteins/genetics ; Methicillin-Resistant Staphylococcus aureus/genetics ; Plasmids/genetics ; Quaternary Ammonium Compounds
Chemical Substances	Anti-Infective Agents, Local ; Antiporters ; Bacterial Proteins ; DNA, Bacterial ; Disinfectants ; Membrane Transport Proteins ; QacB protein, Staphylococcus aureus ; Quaternary Ammonium Compounds ; small multidrug-resistance pump, Staphylococcus aureus ; qacA protein, Staphylococcus aureus (134773-66-3) ; chlorhexidine gluconate (MOR84MUD8E) ; Chlorhexidine (R4KO0DY52L)
Language	English
Publishing date	2013-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1086/673983
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