Pneumococcal acute otitis media aom biology essay

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Q1 Please confirm that given names and surnames have been identified correctly. Q2 Please provide an e-mail address for correspondence purposes. Please check this box or indicate your approval ifyou have no corrections to make to the PDF fileThank you for your assistance. 12 Pneumococcal acute otitis media in infants and children in central3 Romania, 2009–2011: microbiological characteristics and potential4 coverage by pneumococcal conjugate vaccines5 O. Falup-Pecurariu Q1a, E. Leibovitz b,*, A. Mercas a, L. Bleotu a, C. Zavarache a, N. Porat b, 6 R. Dagan b, D. Greenberg b7 a Department of Pediatrics, Children’s Hospital, Faculty of Medicine, Transilvania University, Brasov, Romania8 b Pediatric Infectious Disease Unit, Soroka University Medical Center, Ben-Gurion University, Beer-Sheva, Israel Q291011 1. Introduction12 Acute otitis media (AOM) is the most frequent bacterial disease13 of childhood, affecting millions of children worldwide and14 remaining a major public health problem. 1–3 The most common15 causative agents in AOM are Streptococcus pneumoniae, non-16 typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis, and17 Streptococcus pyogenes. 4–8 Together, S. pneumoniae and NTHi18 account for 60–80% of the AOM pathogens. 9 Antibiotic resistance19 is high in pneumococcal AOM, with penicillin- and amoxicillin-20 non-susceptible strains accounting for 30–70% of cases. 10–16 The21 most commonly encountered S. pneumoniae serotypes in AOM are22 6A, 6B, 14, 19A, 19F, and 23F. 15, 16 The highest antibiotic non-23 susceptibility is found in vaccine serotypes 6A, 6B, 9 V, 14, 19A, 24 19F, and 23F. 11, 12, 15, 1625 Information on antibiotic resistance patterns and serotype26 distribution of S. pneumoniae isolates in infants and young children27 in Romania is limited. In a multinational study, 42% of28 S. pneumoniae AOM isolates from Romania were intermediately29 or fully resistant to penicillin. 17 In three studies investigating30 pneumococcal mucosal and invasive disease isolates inInternational Journal of Infectious Diseases xxx (2013) xxx. e1–xxx. 5A R T I C L E I N F OArticle history: Received 23 November 2012Received in revised form 26 December 2012Accepted 2 February 2013Corresponding Editor: Eskild Petersen, Aarhus, DenmarkKeywords: Acute otitis mediaStreptococcus pneumoniaeAntibiotic resistanceChildrenS U M M A R YObjective: To assess the epidemiological and microbiological characteristics of pneumococcal acute otitismedia (AOM) in children in Brasov, Central Romania, before the introduction of pneumococcal conjugatevaccine (PCV) into the routine national immunization program. Methods: All AOM patients aged <5 years who underwent tympanocentesis or presented with purulentotorrhea of _24 h duration during 2009–2011 were enrolled. results: two hundred and twelve consecutive aom patients had a middle ear fluid (mef) cultureperformed; 99 (46. 6%) episodes occurred in <12 months age. one eleven (52. 4%)episodes culture-positive. was performed 142 spontaneousotorrhea cultures 70 patients. overall, 114 pathogens recovered: streptococcus pneumoniae wasthe most common isolate (81 isolates, 70. 3% all culture-positive episodes), followed by non-typeablehaemophilus influenzae (26, 20. 7%), pyogenes (5, 4. 5%), moraxella catarrhalis (2, 1. 8%). antibiotic susceptibility serotyping for 48 (59. 3%) s. isolates: 45 (93. 8%)were non-susceptible to penicillin (minimal inhibitory concentration (mic) _2. 0 mg ml 24, 53. and37 (77. 1%) isolates ceftriaxone mic values _0. 5 (16> 2. 0 mg/ml). S. pneumoniaenon-susceptibility rates to trimethoprim–sulfamethoxazole, erythromycin, and clindamycin were75. 0%, 58. 3%, and 35. 4%, respectively. All isolates were susceptible to chloramphenicol. Multidrugresistance was found in 33 (68. 7%) isolates. The most common S. pneumoniae serotypes were 19F (14, 29. 2%), 6B (8, 16. 7%), 23F (8, 16. 7%), and 14 (6, 12. 5%). Serotype 19A was found in three (6. 2%) patientsand 6A in two (4. 1%). Non-PCV13 serotypes represented six (12. 6%) of all serotypes (four of them nonsusceptibleto penicillin). Thirty-six (75. 0%) isolates were potentially covered by PCV7, 37 (77. 0%) byPCV10, and 42 (87. 5%) by PCV13. Conclusions: (1) S. pneumoniae was the most prevalent pathogen, with frequent antibiotic resistance andmulti-resistance patterns; (2) most pneumococcal AOM and multidrug-resistant episodes could beprevented by PCVs. _ 2013 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.* Corresponding author. G ModelIJID 1656 1–5Please cite this article in press as: Falup-Pecurariu O, et al. Pneumococcal acute otitis media in infants and children in central Romania, 2009–2011: microbiological characteristics and potential coverage by pneumococcal conjugate vaccines. Int J Infect Dis (2013), http://dx. doi. org/10. 1016/j. ijid. 2013. 02. 002Contents lists available at SciVerse ScienceDirectInternational Journal of Infectious Diseasesjou r nal h o mep ag e: w ww . elsevier . co m /loc ate/ijid1201-9712/$36. 00 – see front matter _ 2013 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. http://dx. doi. org/10. 1016/j. ijid. 2013. 02. 00231 HIV-negative and HIV-positive infants and children in northeast-32 ern Romania, high rates of recovery of serotypes 19A and 23F and33 of multidrug-resistant (MDR) organisms were reported. 18–2034 Recently, high rates of colonization with S. pneumoniae (reaching35 71% in children 13–24 months of age) accompanied by high36 resistance rates to most of the commonly used antibiotic drugs37 were reported among healthy and sick infants and children38 <5 years old in central romania. 2139 active and continuous surveillance of the microbiology and40 antibiotic susceptibility patterns aom pathogens romania is41 important, particularly during period preceding introduc-42 tion pneumococcal conjugate vaccine (pcv). aims the43 present study were to assess: (1) overall distribution of44 otopathogens their resistance patterns; (2) pcv45 coverage s. pneumoniae middle ear fluid (mef) isolates brasov, 46 romania, 2009–2011. 47 2. patients methods48 we conducted a prospective epidemiological between49 january 1, 2009 december 31, 2011, at children’s hospital50 part brasov has population of51 400 000 inhabitants hospital is only medical center52 providing care for infants children city. the53 protocol was approved by institutional review board of54 university transilvania, brasov. informed consent was55 obtained from legal guardians all children. 56 1. procedures57 aged <5 years58 diagnosed with pediatrician, family physician, or59 otolaryngologist. diagnosis done when patients60 presented with: symptoms physical findings consistent61 (fever, irritability, tugging ear, redness and62 bulging tympanic membrane blurring its anatomic63 landmarks); acute illness lasting _7 days. the64 (in addition clinical aom)65 cases where tympanocentesis performed. 66 culture specimens either or67 collection pus draining ears (if _24 h before68 enrollment). tympanostomy tubes excluded69 study. episodes, collected information on the70 patient’s age, sex, ethnicity, type specimen (tympano-71 centesis or pus), history recent72 treatment. data records73 hospital, chart, parent interview. none of74 had been immunized pcv before enrollment. 75 performed otolaryngologist76 (am) as previously described. 7, 1277 bacteriology78 swabs mef aspirates placed mw173 amies transport79 medium (transwab; wire equipment), plated80 immediately trypticase agar containing 5% sheep blood and81 5 mg ml gentamicin, chocolate agar, incubated 35 8c82 48 enriched co2 atmosphere. identification, 83 serotyping, testing antimicrobial penicillin84 ceftriaxone (by e-test, pdm epsilometer, ab biodisk, solna, 85 sweden) erythromycin, clindamycin, chloramphenicol, and86 trimethoprim–sulfamethoxazole (tmp–smx) disk diffusion)87 described elsewhere, accordance the88 laboratory standards institute (clsi) recommenda-89 tions. 22 non-susceptibility _3 classes considered90 multidrug (mdr). serotyping quellung91 reaction. 23 organisms sub-cultured stored _70 8c92 children’ brasov93 further transported air pediatric infectious94 disease unit soroka center, 95 beer-sheva, israel, testing96 carried out. 97 considered susceptible penicillin98 if minimal inhibitory concentration (mic) values were99 _0. 06 ml, intermediate penicillin mic between100 0. 125 0 resistant were101 _2. ml. defined by102 mics between high by103> 2. 0 mg/ml. 104 2. 3. Statistical analysis105 Data were recorded using Microsoft Access office software. The106 statistical analysis was performed using SPSS 17. 0 software. 107 Contingency table analysis for comparing rates between un-108 matched samples was performed using the Chi-square test or109 Fisher’s exact test, as appropriate. The Student independent110 samples t-test was used to compare continuous variables. The111 percentages of serotype coverage were calculated and compared112 between PCV7 (serotypes 4, 6B, 9 V, 14, 18C, 19F, and 23F), PCV10113 (PCV7 plus serotypes 1, 5, and 7F), and PCV13 (PCV10 plus114 additional serotypes 3, 6A, and 19A). All tests were considered115 significant if p-values were <0. 05. 116 3. Results117 During the study period, 212 consecutive infants and young118 children <5 years of age were enrolled. there 120 (56. 6%)119 males. the mean (_ standard deviation) was 18. 0 _ 14. 2 months. ninety-nine (46. 6%) episodes occurred in patients <12 months old121 and 136 (64. 2%) children <2 old. one122 hundred eleven samples (52. 4%) culture-positive. children123 with culture-positive mef older than culture-124 negative (20. 6 15. vs. 4 12. months, p =0. 008). 125 tympanocentesis recorded 142 spontane-126 ous otorrhea 70 patients. no differences the127 proportions spontaneous perforation between with128 culture-negative (38 111, 129 34. 2% 32 101, 31. 7%, 0. 7). 130 a total 114 isolates (76 from 38 from131 specimens) recovered. s. pneumoniae132 most common isolate (81 isolates, 78 episodes, 71. 1% all133 pathogensrecovered 70. 3% all episodes), 134followed by nthi (26, 23; 22. 8% 20. 7%), streptococcus135 pyogenes (5, 5; 4. 4% 5%) moraxella catarrhalis (2, 2; 1. 8%) (table 1). three (1. 137 both pneumoniae isolated. were138 percentages fromtable 1acute otitis media microbiology 212 (111 culture-positive) during2009–2011pathogen no. episodesastreptococcus (70. 3)haemophilus influenzae 23 7)streptococcus 5 (4. 5)moraxella 8)s. + h. 3 (2. 7)culture-positive 111culture-negative 101total 212a percentage is given parenthesis. o. falup-pecurariu et al.> 50% for each antibiotic) and220 MDR was found in 67% of isolates. The most common pneumo-221 coccal serotypes isolated were 23F, 6B, 19F, 14, 6A, and 19A, and222 the potential coverage by PCV7, PCV10, and PCV13 was 66%, 74%, 223 and 80%, respectively. This is consistent with the AOM findings in224 the current study. 225 The major limitation of this study derives from the small226 number of pneumococcal isolates evaluable for antibiotic227 susceptibility testing and serotyping. On the other hand, the data228 presented here from MEF cultures performed in AOM patients229 diagnosed and treated at the Brasov Children’s Hospital are230 additional to previously published information on the pneumo-231 coccal carriage in patients enrolled from daycare centers and232 immunization clinics in the city of Brasov and also from the233 emergency room and surgery department of the hospital (which is234 the only referral pediatric hospital in the whole area and is the235 only site where MEF and nasopharyngeal cultures are per-236 formed). 21 Therefore, we are convinced that these two studies237 from Brasov provide an up-to-date and reliable picture of the local238 pneumococcal burden in infants and young children and the239 antibiotic susceptibility, serotype distribution, and potential240 serotype coverage by PCVs in the city of Brasov and the241 surrounding areas. At the present time, additional limited data242 from nasopharyngeal and MEF pneumococcal isolates obtained243 from infants and young children are available from the244 northeastern (Iasi) and southern (Bucharest) areas of the country245 and provide a similar picture in terms of colonization burden, 246 extremely high antibiotic resistance rates, serotype distribution, 247 and potential PCV coverage. 17–21, 24248 The presented data, together with the additional data from249 northeastern Romania, raise major concerns regarding the250 unskilled used of antibiotics in this country, leading to highTable 2Streptococcus pneumoniae serotype distribution (in decreasing frequency) for 48acute otitis media episodesSerotype No. episodes (%) MDR19F 14 (29. 2) 13 (92. 9%)23F 8 (16. 7) 8 (100%)6B 8 (16. 7) 8 (100%)14 6 (12. 5) -19A 3 (6. 2) 3 (100%)6A 2 (4. 1) 1 (50%)22F 2 (4. 1) -9V 1 (2. 1) -34 1 (2. 1) -9A 1 (2. 1) -7F 1 (2. 1) -Omni-negative 1 (2. 1) -Total 48 33 (68. 7%)MDR, multiple drug resistance. O. Falup-Pecurariu et al. / International Journal of Infectious Diseases xxx (2013) xxx. e1–xxx. e5 e3G ModelIJID 1656 1–5Please cite this article in press as: Falup-Pecurariu O, et al. Pneumococcal acute otitis media in infants and children in central Romania, 2009–2011: microbiological characteristics and potential coverage by pneumococcal conjugate vaccines. Int J Infect Dis (2013), http://dx. doi. org/10. 1016/j. ijid. 2013. 02. 002resistance. Furthermore, the high rate of resistance is of concern in252 terms of the efficacy of current antimicrobial agents in the253 treatment of AOM. 254 Faced with the alarming resistance data presented in this255 study, an intervention program including a major reduction in256 antibiotic use, combined with introduction of routine vaccination257 with PCVs, is much needed in Romania. In France, Cohen et al. 25258 clearly showed that the implementation of a national program of259 reduction of inappropriate antibiotic use markedly contributed to260 the efficacy of PCV7 in reducing the carriage of penicillin-non-261 susceptible pneumococci in children with AOM. In a study262 evaluating the association between antibiotic use in the commu-263 nity and the increase in antibiotic-resistant S. pneumoniae264 carriage in Bedouin children aged <5 years in southern Israel265 from 1998 to 2005, Greenberg et al. 26 examined all the antibiotic266 prescriptions provided from two community primary pediatric267 clinics and reported a decrease by 19% in the total annual268 prescription rates, mainly as a result of a reduction in amoxicillin–269 clavulanate prescriptions. Oral cephalosporins, erythromycin, 270 and penicillin prescription rates decreased significantly as well, 271 but azithromycin prescription rates increased significantly during272 the study period. In parallel, the authors analyzed the273 S. pneumoniae nasopharyngeal carriage in healthy children274 <5 years old from the same communities and were able to275 demonstrate an increase in the proportion of nasopharyngeal276 S. pneumoniae with penicillin MICs _1. 0 mg/ml from 8% to 21% and277 significant increases in resistance to clindamycin, erythromycin, 278 and tetracycline and also in multidrug resistance. The authors279 suggested an association between the increased carriage of MDR280 S. pneumoniae and the increased azithromycin consumption, and281 cautioned that a reduction in the total antibiotic use may not be282 sufficient as long as antibiotics with a high potential for the283 promotion of multidrug resistance, like azithromycin, continue to284 be used widely. 26285 The introduction of the 7-valent conjugate PCV (PCV7)286 had a major role in the reduction of invasive and mucosal287 disease rates caused by S. pneumoniae and of the antimicrobial288 resistance of the isolated organisms, and also, although less289 impressive, in the reduction of nasopharyngeal colonization290 and AOM cases caused by this pathogen. 27–32 In our study, the291 good coverage of overall pneumococcal serotypes and also of292 MDR pneumococcal isolates by all PCVs, and in particular by293 PCV13 (87. 5% and 100%, respectively), are important and294 encouraging findings. 295 PCV7 was registered in Romania in September 2007, but is not296 yet included in the routine immunization program for Romanian297 infants and children. Initiation of a national immunization298 program is urgently needed in order to achieve a reduction in299 pneumococcal disease in general and of antibiotic-resistant and300 MDR pneumococcal AOM in particular. 301 Acknowledgements302 This study was supported by a European Society of Infectious303 Diseases (ESPID) Research Grant (2010). 304 Conflict of interest: Prof. Ron Dagan has received grants/research305 support from Berna/Crucell, Pfizer, MSD, and Protea; has been a306 scientific consultant for GlaxoSmithKline, Pfizer, NASVAX, and307 MSD and a speaker for Berna/Crucell, GlaxoSmithKline, and Pfizer; 308 he is a shareholder in Protea/NASVAX. All other authors report no309 conflict of interest.