The role of respiratory syncytial virus and other viral pathogens in acute otitis media

We utilized recently developed enzyme immunoassay techniques to examine the role of selected viruses in the etiology of acute otitis media. Viral pathogens were found in middle ear fluids obtained from 13 (24%) of 53 children with acute otitis media; respiratory syncytial virus accounted for ten of the 13 viral agents identified. In addition, respiratory syncytial viral antigen was found in nasopharyngeal washings obtained from 15 of the 53 children. Seven of these children had RSV identified as the sole middle ear pathogen, whereas six children had otitis caused by Streptococcus pneumoniae as either the sole middle ear pathogen or in combination with RSV. Similarly, all three children with respiratory infections caused by influenza virus had ear infections caused by bacterial pathogens, either alone or in combination with influenza virus. These findings suggest that, in patients with viral respiratory infection, coexisting acute otitis media may be associated with the recovery of either viruses or bacteria from the middle ear exudates.     

Effect of viral respiratory tract infection on outcome of acute otitis media

We prospectively studied 271 infants and children (2 months to 7 years of age) with acute otitis media (AOM) for viral and bacterial causes, outcome at the end of therapy, and frequency of recurrence within 1 month. Comprehensive virologic methods, including viral antigen detection, cell culture, and serologic studies, were used to diagnose viral infection of the respiratory tract, middle ear, or both. Evidence of viral infection was found in 46% (124/271) of patients with AOM. Sixty-six patients (24%) had virus or viral antigen in the middle ear fluid; 50 of these patients (76%) also had bacteria in middle ear fluid, and 16 (24%) had virus alone. More patients with AOM and combined bacterial and viral infection (51%) had persistent otitis (3 to 12 days after institution of antibiotic treatment), compared with those with only bacterial otitis (35%; p = 0.05) or patients with only viral infection (19%; p less than 0.01). Of patients with only viral infection, 4 of 10 with virus in middle ear fluid had persistent otitis, compared with none of 11 patients who had virus only in nasal wash specimens or whose viral infection was diagnosed only by serologic studies. Our data suggest that viruses interact with bacteria and that concurrent viral infection can significantly worsen the clinical course of bacterial AOM. The presence of virus in middle ear fluid may contribute to the pathogenesis and outcome of bacterial AOM. The mechanism of these interactions deserve further investigation.     

Respiratory virus infection as a cause of prolonged symptoms in acute otitis media

We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.     

Acute otitis media and respiratory virus infections

We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.     

Presence of viral nucleic acids in the middle ear: acute otitis media pathogen or bystander?

Viruses play an important role in acute otitis media (AOM) pathogenesis, and live viruses may cause AOM in the absence of pathogenic bacteria. Detection of AOM pathogens generally relies on bacterial culture of middle ear fluid. When viral culture is used and live viruses are detected in the middle ear fluid of children with AOM, the viruses are generally accepted as AOM pathogens. Because viral culture is not sensitive and does not detect the comprehensive spectrum of respiratory viruses, polymerase chain reaction assays are commonly used to detect viral nucleic acids in the middle ear fluid. Although polymerase chain reaction assays have greatly increased the viral detection rate, new questions arise on the significance of viral nucleic acids detected in the middle ear because nucleic acids of multiple viruses are detected simultaneously, and nucleic acids of specific viruses are detected repeatedly and in a high proportion of asymptomatic children. This article first reviews the role of live viruses in AOM and presents the point-counterpoint arguments on whether viral nucleic acids in the middle ear represent an AOM pathogen or a bystander status. Although there is evidence to support both directions, helpful information for interpretation of the data and future research direction is outlined.     

Microbiology of otitis media in Costa Rican children, 1999 through 2001

BACKGROUND: Because of the increasing number of resistant middle ear pathogens and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis media (FOM). METHODS: Between 1999 and 2001 middle ear fluid (MEF) was collected from 276 Costa Rican patients. S. pneumoniae serotyping and pulsed field gel electrophoresis analysis was done on available strains. RESULTS: Among the total study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM patients. Overall S. pneumoniae (88 strains) was the most common pathogen isolated followed by Haemophilus influenzae (41 strains) and Streptococcus pyogenes (10 strains). H. influenzae was the most common agent in FOM patients (P = 0.015). Beta-lactamase production was observed in 3 of 41 (7%) H. influenzae strains and 3 of 3 (100%) Moraxella catarrhalis strains. Penicillin-nonsusceptible S. pneumoniae strains were more common in FOM (64%) and ROM (63%) patients than in AOM (42%) patients (P = 0.05). S. pneumoniae serotype 19F was the most prevalent serotype, mainly within one distinct clone. CONCLUSIONS: Overall S. pneumoniae serotype 19F was the most common isolate from the middle ear fluid of Costa Rican children. Beta-lactamase-negative H. influenzae was the most prevalent in the subpopulation of patients with FOM. S. pyogenes was the third most common isolate and M. catarrhalis was uncommon.     

Simultaneous recovery of bacterial and viral pathogens from cerebrospinal fluid

Mixed bacterial infection in meningitis is well-documented, but there have been few previous reports of mixed viral-bacterial meningitis. A retrospective analysis of the bacterial and viral cerebrospinal fluid (CSF) cultures from a 1-year period in a 315-bed children's hospital revealed 5 patients with mixed viral-bacterial meningitis among 276 patients with viral and/or bacterial culture-positive meningitis. These 5 accounted for 2.8% of the patients with positive CSF viral cultures and 4.8% of those with positive CSF bacterial cultures. All of the viruses were identified as enteroviruses, and the bacteria were Group B Streptococcus, Group D Salmonella, Streptococcus pneumoniae, Haemophilus influenzae type b and Staphylococcus aureus. The ages of the patients ranged from 10 days to 22 years. The clinical course of each of the illnesses was typical of bacterial meningitis. This relatively high frequency of mixed viral-bacterial meningitis could affect the utility of rapid viral diagnostic tests for CSF viruses.     

Etiology of acute lower respiratory tract infections in Gambian children: I. Acute lower respiratory tract infections in infants presenting at the hospital.

Ninety infants less than 1 year of age with pneumonia and 43 control infants were investigated for viral and chlamydial infection with the use of culture and serology and for bacterial infection with the use of blood cultures, lung aspirates, antibody assays and antigen detection procedures. One or more potential pathogens were identified in 62 (69%) cases with pneumonia and in 12 (28%) controls. Infection by respiratory viruses was identified in 42 (49%) cases and in 8 (19%) controls. Respiratory syncytial virus was the commonest pathogen identified and was found in 32 cases (37%). Bacterial infections were also common, being found in 27 (30%) cases and 3 (7%) controls, and predominantly involved Streptococcus pneumoniae (20%) or Haemophilus influenzae (11%). Bacterial infections were associated with raised white blood cell counts and were identified more often by antigen detection procedures (68%) than by culture of blood or lung aspirates (34%) or by serology (33%). Mixed viral-bacterial infections were identified in 13 cases (15%). Infection with Chlamydia trachomatis was diagnosed in 2 infants with acute lower respiratory tract infection and in 1 control infant.     

儿童病毒性脑炎多中心诊断治疗研究

目的　探讨儿童病毒性脑炎的诊断与治疗问题。方法　以多中心、前瞻开放、随机对比方法观察儿童病毒性脑炎的临床症状、体征及脑脊液常规生化 ;以聚合酶链反应 (PCR)技术检测儿童病毒性脑炎脑脊液病原 ;在综合治疗的前提下 ,以单一抗病毒药物治疗儿童病毒性脑炎。结果　本组 14 3例病毒性脑炎中发热 134例(93 7% ) ,头痛 86例 (6 4 7% ) ,呕吐 87例 (6 0 8% ) ,呕吐伴头痛 5 9例 ,惊厥发作 4 7例 (32 9% ) ,以全身阵挛发作为主 ;有精神症状 87例 (6 0 8% ) ,意识障碍 2 5例 (17 5 % ) ,颈抵抗 4 6例 (32 2 % ) ,运动障碍 2 0例 ,锥体束征 9例 ;脑脊液常规生化检查异常 90例 ,其中 86例白细胞增多 ,16例蛋白定量增高。 14 3例均做了脑脊液病原学检测 ,病毒阳性 84例 (5 8 7% ) ,其中肠道病毒阳性 4 0例 ,DNA病毒阳性 4 4例 ,另外还检测出了 6例支原体。在症状、体征和脑脊液常规生化检查阳性的 4 6例中 ,脑脊液病毒学阳性 2 6例 (5 6 5 % ) ,在症状和脑脊液常规生化检查阳性者 4 4例中 ,脑脊液病毒学阳性 2 3例 (5 2 3% )。在脑脊液病原学不明的情况下 ,在综合治疗的基础上 ,三种抗病毒药物单药抗病毒治疗临床疗效无差别。结论　除常规诊断条件外 ,病毒病原学检查十分重要 ,抗病毒治疗以覆盖更广     

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目的 了解儿童急性下呼吸道感染(ALRTI)病毒病原学特点.方法 2007年3月至2008年2月,在北京儿童医院内科就诊及住院治疗的临床诊断为ALRTI的患儿共572例.对每例患儿在就诊当日或次日采集鼻咽吸取物1份,采用逆转录(RT)-PCR方法进行常见呼吸道病毒核酸检测,包括呼吸道合胞病毒(RSV)、鼻病毒(RV)、副流感病毒(PIV)1～4型、甲型及乙型流感病毒(IFA、IFB)、腺病毒(AdV)、肠道病毒(EV)、冠状病毒(HCoV)、偏肺病毒(hMPV)及博卡病毒(HBoV).结果 572例患儿标本中,444例检出至少1种病毒,总检出率77.6%.各种病毒中,RSV检出率最高,占48.3%,其次是RV(27.1%)和PIV(13.3%).不同年龄组病毒的总检出率差异有统计学意义,<3岁组检出率较高,≥5岁组病毒检出率明显降低.不同年龄组JLRTI病原谱有所不同,<5岁各组主要是RSV、RV、PIV,而≥5岁组则主要为RV、IFV、RSV.572例中,158例(27.6%)检出2种或2种以上病毒,<1岁惠儿混合感染率最高,为40.2%,随年龄增长混合感染率逐渐下降,≥5岁患儿混合感染率仅为14.0%.结论 就诊于北京儿童医院的ALRTI患儿中,5岁以下者ALRTI的主要病毒病原是RSV、RV、PIV;≥5岁则主要为RV、IFV、RSV.     

Otitis media in infants aged 0-8 weeks: frequency of associated serious bacterial disease.

OBJECTIVE: To determine the frequency of serious bacterial infection in well appearing infants aged 0-8 weeks with isolated otitis media (OM). METHODS: Infants with confirmed OM underwent tympanocentesis with middle ear fluid (MEF) culture and complete sepsis evaluation. Enrolled infants were admitted to the hospital for parenteral antibiotics until blood, urine, and CSF cultures were negative for 48 hours. RESULTS: Forty non-toxic appearing infants were enrolled between January 1994 and April 1995, of whom 15 (38%) had a documented rectal temperature > or =38 degrees C. Bacterial pathogens were isolated from MEF cultures in 25 (62.5%) infants. All afebrile infants had negative blood, urine, and cerebrospinal fluid cultures (upper limit (UL) 95% CI 0.11). Only two febrile infants had positive cultures from sites other than the MEF (UL 95% CI 0.36). CONCLUSION: In our study population, previously healthy, non-toxic appearing afebrile infants aged 2-8 weeks and having isolated OM infrequently have an associated serious bacterial infection, suggesting that outpatient treatment with oral antibiotics and close follow-up may be an option. Further studies with large numbers of infants are necessary to confirm this conclusion.     

Bacteriologic and clinical efficacy of one day vs. three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children

BACKGROUND: One dose of intramuscular ceftriaxone has been recently licensed in the United States for the treatment of acute otitis media. However, data regarding the bacteriologic and clinical efficacy of this regimen in the treatment of nonresponsive acute otitis media are incomplete. OBJECTIVES: To determine the bacteriologic and clinical efficacy of a 1-day 50-mg/kg vs. a 3-day 50-mg/kg/day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media in children. PATIENTS AND METHODS: In an open, prospective study 109 patients ages 3 to 36 months with culture-proved, nonresponsive acute otitis media were randomized to receive 1 (n = 49) or 3 (n = 60) 50-mg/kg/day intramuscular ceftriaxone doses, respectively. Middle ear fluid was aspirated for culture by tympanocentesis on the day of enrollment (Day 1); a second tympanocentesis with middle ear fluid culture was performed on Days 4 to 5. Additional middle ear fluid cultures were obtained if clinical relapse occurred after completion of therapy. Bacteriologic failure was defined by positive cultures on Days 4 to 5. Patients were followed until Day 28 after completion of therapy. Susceptibility of the middle ear pathogens was measured by E-test. RESULTS: Organisms recovered (n = 133) were Streptococcus pneumoniae (30 and 35 isolates for the 1-day and 3-day treatment group, respectively), Haemophilus influenzae (26 and 38, respectively) and Moraxella catarrhalis (n = 4). Of the 30 S. pneumoniae isolated from the 1-day group, 27 (90%) and 6 (20%) were nonsusceptible to penicillin and ceftriaxone, respectively; 9 of 27 (33%) were fully resistant to penicillin. Thirty-four (97%) and 6 (17%) of the 35 S. pneumoniae isolated from the 3-day group were nonsusceptible to penicillin and ceftriaxone, respectively; 16 of 34 (47%) were fully resistant to penicillin. Bacterial eradication of all H. influenzae and penicillin-susceptible S. pneumoniae was achieved in both treatment groups. Bacterial eradication of 14 of 27 (52%) and 33 of 34 (97%) penicillin-nonsusceptible S. pneumoniae was achieved in the 1-day and 3-day group, respectively. Seven (50%) of the 14 patients from the 2 groups who did not achieve bacterial eradication did not improve clinically on Days 4 to 5 and required additional ceftriaxone treatment. CONCLUSION: The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media caused by penicillin-resistant S. pneumoniae.     

病毒性脑炎、脑膜炎多病原的探讨

为探讨北主地区病毒性脑炎及脑膜炎的病原学构成,采用微量细胞培养法,应用人胚肺二倍体细胞（ＨＥＦ）、人表此样癌细胞（Ｈｅｐ－２）、猴肾传代细胞（Ｖｅｒｏ）及狗肾传代细胞（ＭＤＣＫ）等４种细胞系对８６例脑炎、脑膜为患儿的脑脊液、粪便及咽试标本进行了病毒分离。结果３６例分离到了病毒,阳性率为４１．８６＾（３６／８６例）,其中肠道病毒３型（ＡｄＶ３）８例,单纯疱疹病毒１例（ＨＳＶ１）７例,阳性率分别为２０     

Analysis of respiratory viral coinfection and cytomegalovirus coisolation in pediatric inpatients

OBJECTIVE: To determine (1) the rates of single infection and coinfection with 7 respiratory viruses in pediatric inpatients undergoing respiratory viral cultures, (2) the rate of cytomegalovirus (CMV) coisolation in these patients and (3) the relationship between these and length of hospital stay. METHODS: A retrospective analysis of all respiratory viral cultures undertaken at the Royal Children's Hospital, Melbourne, Australia during a 4-year period. RESULTS: A total of 6706 respiratory virus cultures were identified, of which 3955 were the first nasopharyngeal or nasal specimen taken within 48 hours of admission from inpatients younger than 18 years of age. A virus was isolated in 1444 (36.5%) specimens. Coinfection was found in only 13 (0.9%) of these culture-positive specimens (0.3% of all 3955 specimens). After adjustment for age and seasonal variation in virus isolation, rates of coinfection were lower than would have been predicted for most respiratory viruses, particularly for respiratory syncytial virus (RSV) with influenza A, and RSV with any other virus. CMV was isolated in 174 (4.4%) specimens. Rates of CMV coisolation with respiratory viruses were lower than predicted from independent infection rates, with clearest evidence for the most common virus, RSV. The length of hospital stay varied between different viruses, but there was no evidence of increased length of stay in patients with coinfection (median, 1.9 days) compared with single infection (median, 2.5 days). The length of stay was longer in patients with CMV, especially when coisolated with a respiratory virus (a median of 3.9 days for coisolation compared with a median of 2.5 days for CMV isolation alone). CONCLUSION: Coinfection with respiratory viruses is rare and in our study occurred less commonly than predicted from the independent virus isolation rates. Coisolation of CMV occurs less commonly than predicted with RSV. CMV coisolation, in contrast to respiratory virus coinfection, is associated with a longer length of stay.     

Clinical role of respiratory virus infection in acute otitis media

The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.     

An open-label, double tympanocentesis study of levofloxacin therapy in children with, or at high risk for, recurrent or persistent acute otitis media

BACKGROUND: Levofloxacin has excellent activity against common respiratory pathogens and therefore is likely to be effective in treating children with persistent or recurrent otitis media. OBJECTIVE: The objective of this study was to assess the efficacy and safety of levofloxacin treatment in the eradication of bacterial pathogens from the middle ear fluid (MEF) of children with, or at high risk for, persistent or recurrent otitis media. METHODS: An open-label multicenter trial was conducted that involved tympanocentesis at entry and selectively 3 to 5 days after starting levofloxacin (10 mg/kg twice a day for 10 days). RESULTS:: Two hundred five children (80% < or =2 years) were enrolled. One child did not have a confirmed diagnosis of acute otitis media and did not return for follow-up visits. Of the remaining 204 children, 94 (46%) had bilateral infection and 63 (31%) were receiving antimicrobials immediately before entry. One hundred five isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus. pyogenes were recovered in pure or mixed cultures. All isolates were susceptible to levofloxacin. During-treatment bacterial eradication from MEF occurred in 88% (78 of 89) of bacteriologically evaluable patients, including 90% (65 of 72) of children < or =24 months of age. Bacteria initially isolated from MEF were eradicated in 31 of 37 (84%) children infected with S. pneumoniae and in 54 of 54 (100%) children infected with H. influenzae. Overall, clinical success rate after therapy was 94% for the total study population and 92% for the bacteriologically evaluable population. Levofloxacin was well tolerated. Vomiting (4%) was the most common treatment-limiting adverse event. CONCLUSIONS: Levofloxacin was safe and effective in treating and eradicating common bacterial pathogens from MEF in children with, or at risk for, recurrent or persistent otitis media.