Association Between Carriage of Streptococcus Pneumoniae and Staphylococcus Aureus in Children
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BRIEF REPORT Association Between Carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children Gili Regev-Yochay, MD Context Widespread pneumococcal conjugate vaccination may bring about epidemio- Ron Dagan, MD logic changes in upper respiratory tract flora of children. Of particular significance may Meir Raz, MD be an interaction between Streptococcus pneumoniae and Staphylococcus aureus, in view of the recent emergence of community-acquired methicillin-resistant S aureus. Yehuda Carmeli, MD, MPH Objective To examine the prevalence and risk factors of carriage of S pneumoniae Bracha Shainberg, PhD and S aureus in the prevaccination era in young children. Estela Derazne, MSc Design, Setting, and Patients Cross-sectional surveillance study of nasopharyn- geal carriage of S pneumoniae and nasal carriage of S aureus by 790 children aged 40 Galia Rahav, MD months or younger seen at primary care clinics in central Israel during February 2002. Ethan Rubinstein, MD Main Outcome Measures Carriage rates of S pneumoniae (by serotype) and S aureus; risk factors associated with carriage of each pathogen. TREPTOCOCCUS PNEUMONIAE AND Results Among 790 children screened, 43% carried S pneumoniae and 10% car- Staphylococcus aureus are com- ried S aureus. Staphylococcus aureus carriage among S pneumoniae carriers was 6.5% mon inhabitants of the upper vs 12.9% in S pneumoniae noncarriers. Streptococcus pneumoniae carriage among respiratory tract in children and S aureus carriers was 27.5% vs 44.8% in S aureus noncarriers. Only 2.8% carried both Sare responsible for common infec- pathogens concomitantly vs 4.3% expected dual carriage (P=.03). Risk factors for tions. Carriage of S aureus and S pneu- S pneumoniae carriage (attending day care, having young siblings, and age older than moniae can result in bacterial spread and 3 months) were negatively associated with S aureus carriage. endogenous infections.1-3 Streptococ- Conclusions Streptococcus pneumoniae carriage, specifically of vaccine-type strains, cus pneumoniae is carried in the naso- is negatively associated with S aureus carriage in children. The implications of these pharynx by most children at least once findings in the pneumococcal vaccine era require further investigation. during early childhood1 but not fre- JAMA. 2004;292:716-720 www.jama.com quently by adults.4 Staphylococcus au- reus is carried by 10% to 35% of chil- We investigated the possible asso- son in 53 participating primary care pe- dren5-7 and by approximately 35% of the ciation between the 2 pathogens by diatric clinics of a major health main- general adult population.3 Staphylococ- studying their prevalence and risk fac- tenance organization (Maccabi cus aureus is carried most consistently tors for carriage in young children in a Healthcare Services, Tel-Aviv) were en- in the nares. region where pneumococcal conju- rolled. The clinics were located in 4 Various studies have explored bac- gate vaccination is not practiced. large cities in the central district of Is- terial interference—the suppression of rael, inhabited by a middle-class Jew- one species by another.8-11 However, METHODS studies examining possible interfer- The study was approved by the Sheba Author Affiliations: Sheba Medical Center, Tel ence between S aureus and S pneumo- Medical Center Ethics Committee, Ra- Hashomer (Drs Regev-Yochay, Rahav, and Rubin- stein and Ms Derazne), and Sourasky Medical Center niae are noticeably absent. An associa- mat-Gan, Israel. Informed consent was (Dr Carmeli), Sackler School of Medicine, Tel-Aviv Uni- tion between these 2 pathogens may obtained from all parents. versity, and Tel-Aviv, Israel; and Soroka University Medical Center and Faculty of Health Science, Ben Gu- suggest epidemiologic changes that rion University of the Negev, Beer-Sheva, Israel could follow widespread vaccination Study Population (Dr Dagan). Corresponding Author: Gili Regev-Yochay, MD, In- with pneumococcal conjugate vac- During February 2002, children aged fectious Disease Unit, Sheba Medical Center, Ramat- cines. 40 months or younger seen for any rea- Gan, Israel 52621 ([email protected]). 716 JAMA, August 11, 2004—Vol 292, No. 6 (Reprinted) ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 ASSOCIATION OF S PNEUMONIAE AND S AUREUS IN CHILDREN ish population. Each child was in- coccus aureus was identified by mor- RESULTS cluded once; accompanying adults phology, -hemolysis, catalase, DNA- A total of 790 children (90% of chil- (usually parents) were also screened. ase, and coagulase production. dren approached) aged 5 days to 40 None of the children or their contacts months (median, 1.3 years) were received pneumococcal vaccine. Statistical Analysis screened. Fifty-five percent were male. We expected 15% of children to carry A total of 6.1% came for healthy Study Design S aureus and 50% to carry S pneumo- check-up visits and 80% were diag- Nasopharyngeal and nasal swabs were niae. To detect a difference of at least nosed as having a respiratory tract in- obtained from children and their accom- 7% in S aureus carriage rates among S fection. Chronic or recurrent disease (ie, panying adults, who also responded to pneumoniae carriers and noncarriers asthma, recurrent otitis media, recur- an interviewer-administered question- with ␣=.05 and 80% power, a sample rent pneumonia, or skin disorders) was naire including demographic character- size of 353 children in each group was present in 27.8%. istics, number of young siblings (aged Ͻ6 needed. Staphylococcus aureus and S pneumo- years), day care attendance, prior anti- Odds ratios (ORs) and Fisher exact niae were isolated in 80 children biotic treatment, and smoking habits of tests were calculated to assess risk fac- (10.1%) and 340 children (43.0%), re- family members. The physician’s diag- tors for carriage of each organism in- spectively. The proportion of vaccine- nosis on the screening day and medical cluding age, sex, young siblings, dwell- type strains among S pneumoniae car- and immunization histories were ob- ing density, passive smoking, day care riers was 74.2%. Staphylococcus aureus tained from patients’ files. The diag- attendance, respiratory tract infection carriage among S pneumoniae carriers noses were categorized as respiratory in- diagnosis, chronic and recurrent dis- was 6.5% vs 12.9% in S pneumoniae fections, skin diseases (including eases, S pneumoniae or S aureus car- noncarriers. Streptococcus pneumoniae infections), other infections (including riage by the acccompanying adult, ste- carriage among S aureus carriers was urinary tract infections and enteric roid treatment, number of clinic visits 27.5% vs 44.8% in S aureus noncarri- infections), and noninfectious diag- and hospitalization in the last 6 months, ers. If carriage of the 2 organisms were noses. and antibiotic treatment in the last independent (ie, occurring at random), month. Mantel-Haenszel common ORs the expected dual carriage would be Laboratory Procedures and the Breslow-Day test for homoge- 4.3%. However, dual carriage was found Nasopharyngeal cultures were ob- neity were used to control for possible in only 22 children (2.8%) (OR, 0.47; tained with a rayon-tipped wire swab confounding variables (age and day care 95% confidence interval [CI], 0.28- and nasal cultures of both nares were attendance). 0.78; P=.03 by Fisher exact test). obtained with a sterile cotton polyes- A multivariate logistic regression Seven hundred four adults (621 ter swab. Swabs were placed in Amies model with stepwise backward elimi- mothers [88%], 77 fathers, and 6 other transport medium (Copan, Brescia, nation was performed separately for family members) aged 18 to 45 years Italy). All specimens were processed each pathogen. Variables with PϽ.10 (median, 30 years) were screened for within 6 hours. in the univariate analysis were in- S aureus nasal carriage and 693 for both Nasopharyngeal swabs for S pneumo- cluded. Interactions of S pneumoniae pathogens. Staphylococcus aureus and niae isolation were streaked onto tryp- with day care attendance, age, and hav- S pneumoniae were isolated from 182 tic soy agar plates with 5% sheep blood ing young siblings were also included (25.9%) of 704 and 35 (5.1%) of 693, and 5 µg/mL of gentamicin (HyLabs, in the model for S aureus carriage. The respectively. The proportion of vaccine- Rehovot, Israel) and incubated aerobi- criterion for entering into the model was type strains among S pneumoniae car- cally at 35°C in 5% CO2-enriched air. a score statistic of P=.05. A Wald sta- riers was 66.7%. Staphylococcus au- Suspect colonies were isolated and iden- tistic of P=.10 was used to remove a reus carriage among adults was similar tified according to National Commit- variable from the model. −2 Log like- in S pneumoniae carriers and noncarri- tee for Clinical Laboratory Standards lihood, the Nagelkerke R2, and the Hos- ers (25.7% and 25.3%, respectively), recommendations.12 Serotyping of mer-Lemeshow test were used to as- and S pneumoniae carriage was similar S pneumoniae was performed using an- sess goodness of fit. Risk factors were in S aureus carriers and noncarriers tisera (Statens Serum Institute, Copen- checked for confounding and collinear- (5.1% and 5.0%, respectively). Dual car- hagen, Denmark). Vaccine types were ity. Cross-validation was used to as- riage was found in 1.3%, the same as defined as serotypes included in the cur- sess overfitting. All tests used were the expected prevalence (OR, 1.02; 95% rent 7-valent conjugate vaccine as well 2-tailed, and PϽ.05 was considered sta- CI, 0.47-2.23; P=.96 by Fisher exact as the cross-reactive types (ie, sero- tistically significant. Computations were test). groups 4, 6, 9, 14, 18, 19, and 23). performed with SPSS software, ver- The highest S aureus carriage rate Nasal swabs for S aureus isolation sion 11.0 (SPSS Inc, Chicago, Ill) and (30%) was observed in children aged were streaked onto tryptic soy agar S-Plus, version 6.2 (Insightful Corp, Se- 3 months or younger, in whom S pneu- plates with 5% sheep blood.