Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children: implications for the use of heptavalent pneumococcal conjugate vaccine. (Research).We assessed the prevalence of Streptococcus pneumoniae Streptococcus pneu·mo·ni·ae n. Pneumococcus. Streptococcus pneumoniae Microbiology A pathogenic streptococcus with 90 serotypes associated with pneumonia, bacteremia, meningitis Transmission Person to person Incidence serotypes in the nasopharynx nasopharynx /na·so·phar·ynx/ (-far´inks) the part of the pharynx above the soft palate.nasopharyn´geal na·so·phar·ynx n. of healthy children, antimicrobial antimicrobial /an·ti·mi·cro·bi·al/ (-mi-kro´be-al) 1. killing microorganisms or suppressing their multiplication or growth. 2. an agent with such effects. susceptibility patterns, risk factors for carriage, and the coverage of heptavalent Hep`tav´a`lent a. 1. (Chem.) Having seven units of attractive force or affinity; - said of heptad elements or radicals. pneumococcal conjugate vaccine Pneumococcal conjugate vaccine is a vaccine used to protect infants and young children against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). . In 2,799 healthy infants and children, the S. pneumoniae carrier rate was 8.6% (serotypes 3, 19F, 23F, 19A, 6B, and 14 were most common). Most pneumococci (69.4%) were resistant to one or more antimicrobial classes. The rate of penicillin resistance was low (9.1%); macrolide resistance was high (52.1%). Overall, 63.2% of the isolates belonged to strains covered by the heptavalent pneumococcal vaccine pneu·mo·coc·cal vaccine n. A vaccine containing purified capsular polysaccharide antigen from the most common infectious types of Streptococcus pneumoniae, used to immunize against pneumonococcal disease. . This percentage was higher in children <2 years old (73.1%) and in those ages 2-5 years (68.9%). Sinusitis sinusitis Inflammation of the sinuses. Acute sinusitis, usually due to infections such as the common cold, causes localized pain and tenderness, nasal obstruction and discharge, and malaise. in the previous 3 months was the only risk factor for carrier status; acute otitis media Acute otitis media Inflammation of the middle ear with signs of infection lasting less than three months. Mentioned in: Myringotomy and Ear Tubes acute otitis media was the only risk factor for the carriage of penicillin-resistant S. pneumoniae. Most isolated strains are covered by the heptavalent conjugate vaccine A conjugate vaccine is created by covalently attaching a poor antigen to a carrier protein, thereby conferring the immunological attributes of the carrier on the attached antigen. , especially in the first years of life, suggesting that its use could reduce the incidence of pneumococcal pneumococcal /pneu·mo·coc·cal/ (-kok´al) pertaining to or caused by pneumococci. disease. ********** The nasopharynx of children has resident microbial microbial pertaining to or emanating from a microbe. microbial digestion the breakdown of organic material, especially feedstuffs, by microbial organisms. flora that do not usually harm the child but, in some cases, constitute a reservoir of pathogens implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. in respiratory tract infections Noun 1. respiratory tract infection - any infection of the respiratory tract respiratory infection infection - the pathological state resulting from the invasion of the body by pathogenic microorganisms and invasive diseases (1,2). The bacteria carried in the nasopharynx of healthy children reflect the infection-causing strains currently circulating in the community (3), and so studies of the prevalence of different pathogens and their resistance patterns can provide useful indications for more rational therapeutic and preventive strategies. The asymptomatic nasopharyngeal nasopharyngeal pertaining to the nasal and pharyngeal cavities. nasopharyngeal meatus see nasopharyngeal meatus. nasopharyngeal spasm see reverse sneeze. carriage of Streptococcus pneumoniae is widely prevalent in young children and has been related to the development of disease and the spread of the pathogen Pathogen Any agent capable of causing disease. The term pathogen is usually restricted to living agents, which include viruses, rickettsia, bacteria, fungi, yeasts, protozoa, helminths, and certain insect larval stages. (4,5); furthermore, nasopharyngeal colonization colonization, extension of political and economic control over an area by a state whose nationals have occupied the area and usually possess organizational or technological superiority over the native population. by antibiotic-resistant S. pneumoniae has steadily increased over the last few years (6,7). Antibiotic-resistant strains are more often carried by infants and young children than adults and belong to a limited number of serotypes that are also some of the most common causes of invasive pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children. pe·di·at·ric adj. Of or relating to pediatrics. diseases (8-10). A heptavalent conjugate vaccine, which includes the most common serotypes involved in invasive diseases, effectively induces protection against pneumococcal nasopharyngeal carriage (11,12). However, while the vaccine is statistically effective in preventing carriage of vaccine-related strains, a number of reports show an increase in the percentage of nonvaccine strains in immunized patients (13,14). We assessed the prevalence of different S. pneumoniae serotypes in the nasopharynx of healthy children attending day-care centers and primary schools, determined their antimicrobial susceptibility to a wide range of therapeutic compounds, identified the risk factors for carrier status, and defined the possible coverage provided by the heptavalent pneumococcal conjugate vaccine during the first years of life. Patients and Methods Study Population From April 15 through June 15, 2000, a single nasopharyngeal specimen per child was obtained from children attending day-care centers and the first years of primary schools in 13 Italian cities (3 northern, 4 central, 6 southern). Only one pediatrician, belonging to the main pediatric department in each city, was responsible for the study. Two day-care centers (one for infants and children [less than or equal to] 3 years of age and one for children ages 4-5 years) and one primary school (children ages 6-7 years) were also included. All of the children attending each participating center were considered eligible unless they had an underlying chronic illness (immunologic diseases; neoplastic neoplastic /neo·plas·tic/ (ne?o-plas´tik) 1. pertaining to a neoplasm. 2. pertaining to neoplasia. neoplastic pertaining to neoplasia or a neoplasm. disorders; renal, cardiac, hepatic, or hematologic hematological, hematologic pertaining to or emanating from blood cells. hematological tests total and differential white cell counts, hematocrit estimation, erythrocyte count. diseases; bronchodysplasia; Down syndrome Down syndrome, congenital disorder characterized by mild to severe mental retardation, slow physical development, and characteristic physical features. Down syndrome affects about 1 in every 730 live births and occurs in all populations equally. ; chronic otitis media Chronic otitis media Inflammation of the middle ear with signs of infection lasting three months or longer. Mentioned in: Myringotomy and Ear Tubes chronic otitis media with effusion effusion /ef·fu·sion/ (e-fu´zhun) 1. escape of a fluid into a part; exudation or transudation. 2. effused material; an exudate or transudate. ) or even a mild acute upper or lower respiratory tract infection While often used as a synonym for pneumonia, the rubric of lower respiratory tract infection can also be applied to other types of infection including lung abscess, acute bronchitis, and emphysema. at the time of enrollment. The study protocol was approved by the ethics committees of the pediatric departments in charge of health control of the day-care centers and schools in each city, and written informed consent was obtained from a parent or guardian of each child. The questionnaires used to obtain demographic and clinical characteristics of the enrolled children were completed by trained reviewers in the presence of parents. The questions included: 1) the duration of breast-feeding breast-feeding /breast-feed·ing/ (brest´fed?ing) nursing; the feeding of an infant at the mother's breast. ; 2) living conditions living conditions npl → condiciones fpl de vida living conditions npl → conditions fpl de vie living conditions living (urban vs. rural); 3) information about previous day-care attendance; 4) the number and age of family members; 5) birth rank; 6) smoking habits of the family members living together; 7) the number and type of respiratory infections (including rhinitis Rhinitis Definition Rhinitis is inflammation of the mucous lining of the nose. Description Rhinitis is a nonspecific term that covers infections, allergies, and other disorders whose common feature is the location of their symptoms. , tonsillitis tonsillitis Inflammatory infection of the tonsils, usually with hemolytic streptococci (see streptococcus) or viruses. The symptoms are sore throat, trouble in swallowing, fever, and enlarged lymph nodes on the neck. , laryngitis laryngitis, inflammation of the mucous membrane of the voice box, or larynx, usually accompanied by hoarseness, sore throat, and coughing. Acute laryngitis is often a secondary bacterial infection triggered by infecting agents causing such illnesses as colds, , acute otitis media, sinusitis, acute bronchitis acute bronchitis Pulmonology A lower RTI–up to 95% of which are viral–that causes reversible bronchial inflammation Clinical Cough, fever, sputum, wheezing, rhonchi DiffDx Asthma, aspergillosis, occupational exposure, chronic bronchitis, sinusitis, , and pneumonia) during the previous 3 months; and 8) the number and type of antimicrobial drugs administered during the previous 3 months. The information was gathered without knowing the child's carrier status. Specimen Collection Nasopharyngeal specimens were obtained by the same trained investigator in each center on the basis of a previously described and validated protocol (15): a Mini-Culturette (Becton Dickinson BD (NYSE: BDX), is a medical technology company that manufactures and sells medical devices, instrument systems and reagents. Founded in 1897 and headquartered in Franklin Lakes, New Jersey, BD employs 27,000 people in nearly 50 countries. , Cockeysville, MD) extra-thin flexible wire swab with its tip bent at an angle of approximately 30 [degrees] was inserted through the mouth and placed 1 to 1.5 inches into the nasopharynx without touching the uvula uvula: see palate. or the tongue and kept in place for at least 5 seconds. The children were not allowed to eat or drink for 3 hours before specimen collection. Microbiologic Procedures The same microbiologic procedures were used by all of the participating centers on the basis of previously validated guidelines (15,16). The nasopharyngeal cultures were injected into Stuart transport medium tubes (Venturi venturi a tube with a decrease in the inside diameter that is used to increase the flow velocity of the fluid and thereby cause a pressure drop; used to measure the flow velocity (a venturimeter) or to draw another fluid into the stream. Transystem, Brescia, Italy), which were sent to the microbiology laboratory of the individual hospitals within 1-3 hours and immediately processed. S. pneumoniae was isolated and identified using standard laboratory procedures (16). The strains were stored in serum-glycerol freezing medium at -80 [degrees] C, and the frozen samples were sent to the University of Genoa's Institute of Microbiology to confirm their identity and to test their antimicrobial susceptibility by Gram strain morphology, catalase reaction catalase reaction (kat´  lās),n the response of bubbling in the presence of hydrogen peroxide given by blood exudates or transudates. , optochin susceptibility, and bile solubility solubility Degree to which a substance dissolves in a solvent to make a solution (usually expressed as grams of solute per litre of solvent). Solubility of one fluid (liquid or gas) in another may be complete (totally miscible; e.g. . The strains were serotyped by their quellung reaction quel·lung reaction n. See Neufeld capsular swelling. with sera produced by the Statens Seruminstitute (Copenhagen, Denmark) according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. established procedures (16). The strains susceptibility to penicillin, amoxicillin amoxicillin /amox·i·cil·lin/ (ah-mok?si-sil´in) a semisynthetic derivative of ampicillin effective against a broad spectrum of gram-positive and gram-negative bacteria. a·mox·i·cil·lin n. , amoxicillin-clavulanic acid, cefotaxime, ceftriaxone ceftriaxone /cef·tri·ax·one/ (cef?tri-ak´son) a semisynthetic, ß–resistant, third-generation cephalosporin effective against a wide range of gram-positive and gram-negative bacteria, used as the sodium salt. , meropenem, erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). , clarithromycin, azithromycin, tetracycline tetracycline (tĕ'trəsī`klēn), any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein , trimethoprim-sulfamethoxazole, rifampicin rifampicin /rif·am·pi·cin/ (rif´am-pi-sin) rifampin. rifampin, rifampicin a derivative of rifamycin; an antibacterial and antifungal agent used in the treatment of mycobacterial infections, actinomycosis and histoplasmosis. , and chloramphenicol chloramphenicol (klōr'ămfĕn`əkŏl'), antibiotic effective against a wide range of gram-negative and gram-positive bacteria (see Gram's stain). It was originally isolated from a species of Streptomyces bacteria. was tested using the agar dilution method described by the National Committee for Clinical Laboratory Standards (16). MICs of the antimicrobial drags were determined using the Sensititre microbroth incorporation technique with an inoculum inoculum /in·oc·u·lum/ (-ok´u-lum) pl. inoc´ula material used in inoculation. in·oc·u·lum n. pl. of approximately [10.sup.5] CFU/mL in a medium of Mueller-Hinton broth supplemented with saponin-lysed horse blood and Factor V. Further details concerning the microbiologic method we used are given in the article describing the results of the Alexander Project (16). All of the laboratory work was carried out in a blinded manner; susceptibility was tested by a technician unaware of the serotypes, and the samples were typed by a technician unaware of the susceptibility results. Data Management and Analysis The association between the characteristics of the children and the carriage of S. pneumoniae was first analyzed by a series of univariate analyses. Then, to control simultaneously for the possible confounding confounding when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies. confounding factor effects of the different variables, the risk of being an S. pneumoniae carrier was estimated by multiple logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. analysis with stepwise stepwise incremental; additional information is added at each step. stepwise multiple regression used when a large number of possible explanatory variables are available and there is difficulty interpreting the partial regression variable selection. The univariate and multivariate The use of multiple variables in a forecasting model. analyses of antibiotics and antibiotic resistance antibiotic resistance, n the ability of certain strains of microorganisms to develop resistance to antibiotics. antibiotic resistance assessed individual drugs as well as all antibiotics together. In both analyses, the association was expressed in odds ratios (OR) and 95% confidence intervals (CI). Logistic regression analyses were made to evaluate the correlates of the carriage of different S. pneumoniae strains. On the basis of previous studies (12,17-19), strains 14, 6, 19, 18, 23, 9, 1, 7, 4, 5, 3, and 24 were considered invasive, and strains 4, 6, 9, 14, 18, 19, and 23 covered by or cross-reactive with the heptavalent vaccine. All of the reported p values are two-sided and refer to a significance level of 0.05. Results Study Participation The study involved 2,799 children, whose demographic and clinical characteristics are shown in Table 1. Most of them lived in an urban area, attended a large day-care center full-time, belonged to small families, and had at least one respiratory tract infection in the previous 3 months. Recovery of S. pneumoniae from Nasopharyngeal Cultures The pneumococcal carrier rate and the recovery of invasive strains or strains covered by the heptavalent vaccine are shown in Table 2. The total S. pneumoniae carrier rate was 242 (8.6%) out of 2,799, with no significant difference between the age groups; the most common strains were 3 (11.6%), 19F (11.2%), 23F (11.2%), 19A (10.7%), 6B (9.9%), and 14 (6.6%). Furthermore, 77.3% of the examined strains belonged to invasive serogroups (with no significant difference between the age groups) and 63.2% to serogroups covered by or cross-reactive with the heptavalent pneumococcal vaccine. The potential coverage related to the use of the heptavalent vaccine was significantly higher in children ages <2 (73.1%) or 2-5 years (68.9%) than in those aged >5 years (51.2%: <2 vs. >5 years: p=0.040; 2-5 vs. >5 yrs: p=0.0008). The proportion of invasive strains covered by the heptavalent vaccine was 153 (81.8%) of 187. Susceptibility Patterns The antibiotic resistance pattern of the S. pneumoniae strains is shown in Table 3. Only 74 strains (30.6%) were susceptible to all of the antibiotics tested, 69 (28.5%) were resistant to one antimicrobial agent, 70 (28.9%) were resistant to two, and 29 (12.0%) to more than two. Only 22 S. pneumoniae isolates (9.1%) were penicillin-resistant: 18 intermediately resistant (MIC 0.1-1.0 [micro]g/mL) and four fully resistant (MIC [greater than or equal to] 2 [micro]g/mL); the serogroups most resistant were 9V (40.9%) and 23F (22.7%). Seventeen (77.3%) of these penicillin-resistant strains were preventable by the heptavalent pneumococcal conjugate vaccine; none of the five strains not covered not covered Health care adjective Referring to a procedure, test or other health service to which a policy holder or insurance beneficiary is not entitled under the terms of the policy or payment system–eg, Medicare. Cf Covered. by the vaccine is usually considered invasive. The incidence of penicillin resistance was significantly higher in younger children (25.9% in children aged <2 years vs. 7.6% in those aged 2-5 years: p=0.024; 25.9% in children aged <2 years vs. 5.9% in those aged >5 years: p=0.007). Resistance to erythromycin, clarithromycin, and azithromycin ([MIC.sub.50] 0.25, [MIC.sub.90] [greater than or equal to] 64) was very common (52.1%, 126 isolates); the most resistant serogroups were 6B (16.7%), 19F (15.9%), 14 (14.3%), and 19A (12.7%). Of these macrolide-resistant strains, 94 (74.6%) were preventable by the heptavalent pneumococcal conjugate vaccine; none of the 32 uncovered strains is usually considered invasive. Although no significant association was found, the macrolide-resistant strains were. more often isolated in children aged <2 years (60.4%) than in those ages 2-5 years (56.3%) or >5 years (44.6%). Fourteen isolates (5.8%) were both penicillin and macrolide resistant. Risk Factors for Nasopharyngeal Carriage of S. pneumoniae Table 4 shows the results of the univariate analysis of the potential risk factors for the nasopharyngeal carriage of S. pneumoniae. One or more episodes of sinusitis in the previous 3 months was the only risk factor for total carrier status and the carriage of both invasive strains and the strains covered by the heptavalent vaccine. None of the other variables was significantly associated with pneumococcal nasopharyngeal carriage, regardless of the strain. Multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. also indicated at least one episode of sinusitis in the previous 3 months as the only risk factor for the nasopharyngeal carriage of S. pneumoniae (total carriers: OR 2.48; 95% CI 1.11-5.0; carriers of invasive strains: OR 3.04; 95% CI 1.23-6.53; carriers of strains covered by the heptavalent vaccine: OR 3.30; 95% CI 1.41-6.83). In terms of antibiotic resistance, univariate analysis identified one or more episodes of acute otitis media in the previous 3 months as the only risk factor (OR, 2.8; 95% CI 1.2-6.8) and an age >5 years as a protective factor (OR, 0.3; 95% CI, 0.11.0) for the carriage of penicillin-resistant S. pneumoniae. Multivariate analysis confirmed the role of a previous history of acute otitis media (OR 2.7; 95% CI 1.0-6.6). Neither univariate or multivariate analysis identified an association between the carriage of macrolide-resistant strains and any risk or protective factor. Discussion S. pneumoniae was carried by 8.6% of the 2,799 healthy children. Possible reasons for this low prevalence, similar to that previously reported by us (15), include the fact that the survey only included healthy children, the subjects were enrolled for a very short time, winter (a period of frequent respiratory illness Noun 1. respiratory illness - a disease affecting the respiratory system respiratory disease, respiratory disorder adult respiratory distress syndrome, ARDS, wet lung, white lung - acute lung injury characterized by coughing and rales; inflammation of the ) was not the season of enrollment, the large sample prevented any focus on specific situations, and the fact that human genetic traits may play a role (15,17,20). Furthermore, although a sampling or laboratory error is unlikely because all of the investigators were carefully pretrained and the microbiologic procedures were monitored throughout the study, some continuing colonization titers may have been below the sensitivity threshold of the culture method (13). The serotypes most frequently colonizing our healthy population (3, 19F, 23F, 19A, 6B, and 14) were those commonly involved in invasive pneumococcal diseases (12,17-19,21), highlighting the importance of nasopharyngeal colonization in the development of serious community infections. The low rate of penicillin resistance (9.1%) and the high rate of macrolide resistance (52.1%) detected in our study population are in contrast to the data reported in other countries (22-25) but consistent with previous Italian reports regarding adults and children with lower respiratory tract infections and invasive diseases (19,26,27). Comparison of the present data with those coming from our previous survey of a similar population of healthy subjects revealed an increased prevalence of antibiotic-resistant pneumococci, especially in children ages <2 years (15). As in other studies, we found that resistance to penicillin was associated with serotypes 9V and 23F, whereas resistance to macrolides was related to a wide range of serotypes (particularly 6B, 19F, 14, and 19A) (19,26,27). Univariate and multivariate analyses indicate that infections of the nasal sinuses and the middle ear may favor S. pneumoniae carriage and may play a role in the spread of the organisms. However, considering that the data on the characteristics of our study population were obtained from parental recollection, the role of the different risk factors in pneumococcal colonization needs to be further confirmed. The protective effect of an age of >5 years on the carriage of penicillin-resistant strains is in agreement with other published data (17). As we have previously observed (15), but unlike other authors' findings (10,28), nasopharyngeal carriage of S. pneumoniae and antibiotic use per se or the type of drug used in the previous 3 months were not related. In our previous survey (15), we found that having one or more older siblings and a history of full-time day-care attendance were risk factors for the nasopharyngeal carriage of S. pneumoniae, whereas living in a rural area was a protective factor. The differences observed in this study may be because of changes in the epidemiologic characteristics of pneumococcal carriage in Italy and confirm the importance of constant local surveillance. Our data on the efficacy of the heptavalent pneumococcal conjugate vaccine indicate that it could have a considerable impact on the incidence of nasopharyngeal carriage and a major effect on invasive and antibiotic-resistant pneumococcal diseases, especially in the first years of life. In conclusion, our study shows that, although nasopharyngeal carriage is low in healthy children, the most common circulating serotypes are invasive and antibiotic resistant. No risk factor other than sinusitis and acute otitis media seems to be related to pneumococcal colonization and to the carriage of penicillin-resistant S. pneumoniae, respectively. The fact that most isolated strains are covered by the heptavalent conjugate vaccine, especially in the first years of life, suggests that its broader use could reduce the incidence of pneumococcal disease.
Table 1. Characteristics of the 2,799 children tested for
nasopharyngeal carriage of Streptococcus pneumoniae,
13 Italian cities, April 15-June 15, 2000
No. of children
Characteristics (% of 2,799)
Male 1,459 (52.1)
Race (white) 2,760 (98.6)
Age
<2 yrs 420 (15.0)
2-5 yrs 1,389 (49.6)
>5 yrs 990 (35.4)
Breast-feeding [greater than or equal to] 3 mo. 1,477 (52.8)
Urban residence 2,537 (90.6)
Full-time child-care attendance (a) 2,571 (91.9)
No. of subjects in each child-care center
<20 927 (33.1)
20-29 1,600 (57.2)
>29 272 (9.7)
No. of siblings
0 752 (26.9)
1 1,450 (51.8)
>2 597 (21.3)
First-born 1,366 (48.8)
Passive smoking 1,320 (47.2)
URTIs in the last 3 mo. (b)
Rhinitis 1,759 (62.8)
Tonsillitis 636 (22.7)
Laryngitis 501 (17.9)
Acute otitis media 558 (19.9)
Acute sinusitis 174 (6.2)
LRTIs in the last 3 mo. (b)
Acute bronchitis 579 (20.7)
Pneumonia 167 (5.9)
Antibiotic therapy in the last 3 mo. (c)
Aminopenicillins 244 (8.7)
Amoxicillin-clavulanate 214 (7.6)
Macrolides 247 (8.8)
Cephalosporins 507 (18.1)
At least one antibiotic 1,032 (36.9)
(a) 5-6 days/week, 6-8 hrs/day.
(b) One or more episodes; URTIs = upper respiratory tract infections;
LRTIs = lower respiratory tract infections.
(c) One or more courses.
Table 2. Recovery of Streptococcus pneumoniae in the nasopharynx
by age, 13 Italian cities, April 15-June 15, 2000
Age group (% of total/age group)
Carriers <2 yrs 2-5 yrs
Total/age group 420 1,389
Total carriers 26 (6.2) 132 (9.5)
Carriers of invasive 20 (74.1) 106 (81.5)
strains
Carriers of strains 19 (73.1) (a) 91 (68.9) (b)
covered by the
heptavalent vaccine
Age group (% of total/age group)
Carriers >5 yrs Total
Total/age group 990 2,799
Total carriers 84 (8.5) 242 (8.6)
Carriers of invasive 61 (71.2) 187 (77.3)
strains
Carriers of strains 43 (51.2) (a,b) 153 (63.2)
covered by the
heptavalent vaccine
(a) Carriers <2 yrs vs. carriers >5 yrs: p=0.040.
(b) Carriers 2-5 yrs vs. carriers >5 yrs: p=0.0008.
Table 3. Antibiotic resistance pattern of Streptococcus pneumoniae
strains, 13 Italian cities, April 15-June 15, 2000
Antibiotic Resistant strains (%)
Penicillin 22 (9.1)
Amoxicillin 0
Amoxicillin-clavulanate 0
Cefotaxime 9 (3.7)
Ceftriaxone 8 (3.3)
Meropenem 12 (4.9)
Azithromycin 126 (52.1)
Clarithromycin 126 (52.1)
Erythromycin 126 (52.1)
Tetracyclin 74 (30.6)
Thrimethoprim-sulphamethoxazole 58 (23.9)
Rifampicin 0
Chloramphenicol 26 (10.7)
Table 4. Univariate analysis of the variables potentially associated
with the nasopharyngeal carriage of Streptococcus pneumoniae
Total carriers
Risk factor ORs (a) 95% CI (b)
Sex 1.0 0.8-1.4
Age, yrs
2-5 0.7 0.1-1.7
>5 1.5 0.9-2.5
Breast-feeding [greater than or equal to] 3 mo. 0.9 0.6-1.4
Urban residence 0.8 0.1-2.2
Full-time day-care attenance 0.4 0.1-1.5
Child-care center [greater than or equal to] 20
subjects 0.9 0.6-1.3
At least one sibling 0.9 0.7-1.3
First-born 1.0 0.8-1.4
Passive smoking 1.0 0.7-1.3
At least one URTIcin the previous 3 mo.
Rhinitis 0.9 0.7-1.3
Tonsillitis 0.8 0.6-1.3
Laryngitis 0.6 0.3-1.1
Acute otitis media 1.3 0.9-1.9
Acute sinusitis 2.3 1.1-4.6 (d)
LRTIs (e) in the previous 3 mo.
Acute bronchitis 0.7 0.4-1.1
Pneumonia 0.8 0.2-2.6
Antibiotic therapy in the previous 3 mo.
Aminopenicillins 0.9 0.6-1.5
Amoxicillin-clavulanate 0.8 0.4-1.3
Macrolides 0.6 0.3-1.1
Cephalosporins 0.9 0.6-1.3
At least one antibiotic 0.8 0.7-1.2
Carriers of invasive
strains
Risk factor ORs 95% CI
Sex 0.9 0.7-1.4
Age, yrs
2-5 1.3 0.8-2.3
>5 0.9 0.5-1.6
Breast-feeding [greater than or equal to] 3 mo. 1.0 0.6-1.7
Urban residence 1.2 0.6-2.6
Full-time day-care attenance 0.8 0.6-1.2
Child-care center [greater than or equal to] 20
subjects 1.2 0.8-1.9
At least one sibling 0.7 0.4-1.2
First-born 1.1 0.8-1.6
Passive smoking 1.0 0.7-1.4
At least one URTIcin the previous 3 mo.
Rhinitis 1.0 0.7-1.5
Tonsillitis 0.9 0.6-1.5
Laryngitis 0.8 0.5-1.5
Acute otitis media 1.5 0.9-2.3
Acute sinusitis 3.1 1.4-6.4 (d)
LRTIs (e) in the previous 3 mo.
Acute bronchitis 0.6 0.3-1.1
Pneumonia 0.4 0.1-3.1
Antibiotic therapy in the previous 3 mo.
Aminopenicillins 1.0 0.5-1.8
Amoxicillin-clavulanate 0.7 0.3-1.5
Macrolides 0.8 0.4-1.6
Cephalosporins 0.8 0.5-1.3
At least one antibiotic 1.0 0.7-1.4
Carriers of strains
covered by the
heptavalent vaccine
Risk factor ORs 95% CI
Sex 0.9 0.7-1.3
Age, yrs
2-5 1.5 0.9-2.7
>5 1.1 0.6-1.9
Breast-feeding [greater than or equal to] 3 mo. 1.1 0.7-1.7
Urban residence 1.5 0.7-2.9
Full-time day-care attenance 1.0 0.7-1.4
Child-care center [greater than or equal to] 20
subjects 1.2 0.8-1.9
At least one sibling 0.7 0.4-1.3
First-born 1.1 0.8-1.6
Passive smoking 1.0 0.7-1.4
At least one URTIcin the previous 3 mo.
Rhinitis 1.0 0.7-1.5
Tonsillitis 1.0 0.6-1.5
Laryngitis 0.8 0.4-1.5
Acute otitis media 1.4 0.9-2.2
Acute sinusitis 3.3 1.6-6.9 (d)
LRTIs (e) in the previous 3 mo.
Acute bronchitis 0.6 0.4-1.1
Pneumonia 0.9 0.2-3.7
Antibiotic therapy in the previous 3 mo.
Aminopenicillins 1.0 0.5-1.8
Amoxicillin-clavulanate 0.8 0.4-1.5
Macrolides 0.7 0.4-1.5
Cephalosporins 0.9 0.6-1.5
At least one antibiotic 1.0 0.7-1.4
(a) OR = odds ratio.
(b) 95%CI= confidence interval.
(c) URTIs= upper respiratory tract infections.
(d) p<0.05.
(e) LRTIs=lower respiratory tract infections.
Acknowledgments We thank Michele Sacco, Ciro Bianchi, and Alessandro Zollo for their substantial contributions to this study. This work was supported in part by an educational grant from Wyeth-Lederle Pharmaceuticals, Italy. Dr. Marchisio is associate professor of pediatrics at the University of Milan The university is a member of the League of European Research Universities. Throughout Milan, the University is normally known as Statale to avoid confusion with other academic institutions in the city. . Her main interests are pediatric infectious diseases infectious diseases: see communicable diseases. , particularly upper respiratory tract infections upper respiratory tract infection URI Infectious disease A nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx, the prototypic URI is the common cold; flu/influenza is a systemic illness involving the URT , antibiotic resistance, and bacterial pathogenesis. References (1.) Mackowiak PA. The microbial flora. N Engl J Med 1982;307:83-93. (2.) Faden H, Stniaevich J, Brodsky L, Bemstein J, Ogra PL. Changes in nasopharyngeal flora during otitis media Otitis Media Definition Otitis media is an infection of the middle ear space, behind the eardrum (tympanic membrane). It is characterized by pain, dizziness, and partial loss of hearing. of childhood. Pediatr Infect Dis J 1990;9:623-6. (3.) Faden H, Dully L, Wasielewski R, Wolf J, Krystofik D, Tung Y, et al. Relationship between nasopharyngeal colonization and the development of otitis media in children. J Infect Dis 1997;175:1440-5. (4.) Eldan M, Leibovitz E, Piglansky L, Raiz S, Press J, Yagupsky P, et al. Predictive value pre·dic·tive value n. The likelihood that a positive test result indicates disease or that a negative test result excludes disease. predictive value a measure used by clinicians to interpret diagnostic test results. of pneumococcal nasopharyngeal cultures for the assessment of nonresponsive acute otitis media in children. Pediatr Infect Dis J 2000;19:298-303. (5.) Givon-Lavi N, Dagan R, Fraser D, Yagupsky P, Porat N. Marked differences in pneumococcal carriage and resistance patterns between day care centers located within a small area. Clin Infect Dis 1999;29:1274-80. (6.) Zenni MK, Cheatham SH, Thompson JM, Reed GW, Batson AB, Palmer PS, et al. Streptococcus pneumoniae colonization in the young child: association with otitis media and resistance to penicillin. J Pediatr 1995;127:533-7. (7.) Rudolph KM, Parkinson AJ, Reasonover AL, Bulkow LR, Parks DJ, Butler JC. Serotype serotype /se·ro·type/ (ser´o-tip) the type of a microorganism determined by its constituent antigens; a taxonomic subdivision based thereon. se·ro·type n. See serovar. v. distribution and antimicrobial resistance patterns of invasive isolates of Streptococcus pneumoniae: Alaska, 1991-1998. J Infect Dis 2000;182:490-6. (8.) Kaplan SL, Mason EO, Barson WJ, Wald ER, Arditi M, Tan TQ, et al. Three-year multicenter surveillance of systemic pneumococcal infections in children. Pediatrics 1998;102:538-45. (9.) Block SL, Harrison CJ, Hedrick JA, Tyler RD, Smith RA, Keegan E, et al. Penicillin-resistant Streptococcus pneumoniae in acute otitis media: risk factors, susceptibility patterns and antimicrobial management. Pediatr Infect Dis J 1995;14:751-9. (10.) Deeks SL, Palacio R, Ruvinsky R, Kertesz DA, Hortal M, Rossi A, et al. Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae. Pediatrics 1999;103:409-13. (11.) Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, et al. Efficacy, safety and immunogenicity immunogenicity /im·mu·no·ge·nic·i·ty/ (-je-nis´it-e) the property enabling a substance to provoke an immune response, or the degree to which a substance possesses this property. of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19:187-95. (12.) Eskola J, Kilpi T, Palmu A, Jokinen J, Haapakoski J, Herva E, et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001;344:403-9. (13.) Dagan R, Muallem M, Melamed R, Leroy O, Yagupsky P. Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization immunization: see immunity; vaccination. with tetravalent tetravalent /tet·ra·va·lent/ (tet?rah-va´lent) having a valence of four. tet·ra·va·lent adj. Having a valence of four; quadrivalent. tetravalent having a valence of four. pneumococcal vaccines conjugated conjugated adj. Conjugate. estrogens, conjugated Warning - Hazardous drug! C.E.S. to either tetanus toxoid Tetanus toxoid Tetanus toxoid is a vaccine used to prevent tetanus (also known as lockjaw). Mentioned in: Clenched Fist Injury tetanus toxoid or diphtheria diphtheria (dĭfthēr`ēə), acute contagious disease caused by Corynebacterium diphtheriae (Klebs-Loffler bacillus) bacteria that have been infected by a bacteriophage. It begins as a soreness of the throat with fever. toxoid toxoid, protein toxin treated by heat or chemicals so that its poisonous property is destroyed but its capacity to stimulate the formation of toxin antibodies, or antitoxins, remains. . Pediatr Infect Dis J 1997;16:1060-4. (14.) Mbelle N, Huebner RE, Wasas AD, Kimura A, Chang I, Klugman KP. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis 1999;180:1171-6. (15.) Principi N, Marchisio P, Schito GC, Mannelli S, the Ascanius Project Collaborative Group. 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J Infect Dis 2001;183:239-46. (18.) Hausdorff WP, Bryant J, Paradiso PR, Siber GR. Which pneumococcal serogroups cause the most invasive disease: implications for conjugate vaccine formulation and use, part I. Clin Infect Dis 2000;30:100-21. (19.) Pantosti A, D'Ambrosio F, Tarasi A, Recchia S, Orefici G, Mastrantonio P. Antibiotic susceptibility and serotype distribution of Streptococcus pneumoniae causing meningitis in Italy, 1997-1999. Clin Infect Dis 2000;31:1373-9. (20.) Gehanno P, Lenoir G, Barry B, Bons J, Boucot I, Berche P. Evaluation of nasopharyngeal cultures for bacteriologic bac·te·ri·ol·o·gy n. The study of bacteria, especially in relation to medicine and agriculture. bac·te assessment of acute otitis media in children. Pediatr Infect Dis J 1996;15:329-32. (21.) Wee-Ling Soh S, Laa Poh C, Tzer Pin Lin RV. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from pediatric patients in Singapore. Antimicrob Agents Chemother 2000;44:2193-6. (22.) Dagan R, Melamed R, Muallem M, Piglansky L, Yagupsky P. Nasopharyngeal colonization in Southern Israel with antibiotic-resistant pneumococci during the first 2 years of life: relation to serotypes likely to be included in pneumococcal conjugate vaccines. J Infect Dis 1996;174:1352-5. (23.) Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau CR, Reingold AL, et al. Increasing prevalence in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. of multidrug-resistant Streptococcus pneumoniae. N Engl J Med 2000;343:1917-24. (24.) Wenzel RP, Edmond MB. Managing antibiotic resistance. N Engl J Med 2000;343:1961-3. (25.) Tomasz A. New faces of an old pathogen: emergence and spread of multidrug-resistant Streptococcus pneumoniae. Am J Med 1999;107(Suppl 1A):55S-62S. (26.) Marchese mar·che·se n. pl. mar·che·si 1. An Italian nobleman ranking above a count and below a prince. 2. Used as the title for such a nobleman. A, Tonoli E, Debbia EA, Schito GC. Macrolide resistance mechanisms and expression of phenotypes among Streptococcus pneumoniae circulating in Italy. J Antimicrob Chemother 1999;44:461-4. (27.) Principi N, Marchisio P. Epidemiology of Streptococcus pneumoniae in Italian children. Acta Paediatr 2000;89:40-4. (28.) Levine OS, Farley M, Harrison LH, Lefkowitz L, Mc Geer A, Schwartz B. Risk factors for invasive pneumococcal disease in children: a population-based case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. in North America North America, third largest continent (1990 est. pop. 365,000,000), c.9,400,000 sq mi (24,346,000 sq km), the northern of the two continents of the Western Hemisphere. . Pediatrics 1999;103:1-5. Address for correspondence: Nicola Principi, Pediatric Department I, University of Milan, Via Commenda 9, 20122 Milan, Italy; fax: 39-02-55195341; e-mail: Nicola.Principi@unimi.it Paola Marchisio, * Susanna Esposito, * Gian Carlo Schito, ([dagger]) Anna Marchese, ([dagger]) Roberts Cavagna, * Nicola Principi, * and the Hercules Project Collaborative Group (1) * University of Milan, Milan, Italy; and ([dagger]) University of Genoa Located in Liguria on the Italian Riviera, the university was founded in 1471. It currently has about 40,000 students, 1,800 teaching and research staff and about 1,580 administrative staff. , Genoa, Italy (1) The Hercules Project Collaborative Group includes: F. Schettini, D. De Mattia (Bari, Italy); G. P. Salvioli, G. Faldella (Bologna, Italy); G. Caramia, E. Ruffini (Ancona, Italy); E. Reali (Cinisello Balsamo Ci·ni·sel·lo Bal·sa·mo A city of northern Italy, a suburb of Milan. Population: 72,200. , Italy); R. Longhi (Como, Italy); G. Bona (Novara, Italy); A. Guarino, F. Albano (Napoli, Italy); R. Malvicini (Fidenza, Italy); L. Ziino (Palermo, Italy); I. Barbed, T. Corona (Messina, Italy); P. Pusceddu (Cagliari, Italy); T. Meloni (Sassari, Italy); G. Saggese, and M. Migliaccio (Pisa, Italy). |
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