Let's Reexamine the Treatment of URIs

pdnews@elsevier.com

The data from three recent studies should prompt us to reexamine our approach to the management of upper respiratory infections in children.

Guidelines from the American Academy of Pediatrics recommend antimicrobial treatment for children with upper respiratory symptoms lasting longer than 10-14 days or for those with severe symptoms, including a high fever and toxicity (Pediatrics 2001;108:798-808). The Sinus and Allergy Health Partnership Guidelines—to which I contributed—also advised antimicrobial treatment for children with signs and symptoms of viral upper respiratory infection (URI) for more than 10 days or worsening symptoms after 5-7 days (Int. J. Pediatr. Otorhinolaryngol. 2002;63:1-13).

Now data suggest that we perhaps should consider antibiotic treatment only for children whose symptoms are worsening after 10 days.

The recommendation to treat rhinorrhea beyond 10 days with antibiotics as presumptive bacterial sinusitis requires a subjective judgment, and is based on small data sets.

This is problematic in an era in which we're trying to limit antimicrobial use to times when there is definite benefit. It's also been difficult to follow in practice, because parents often bring a child in who has had symptoms for fewer than 10 days. We're not supposed to treat at that point unless they have acute toxicity, but there can be a lot of real or perceived pressure to prescribe.

In fact, the 10-day rule appears to derive from a 40-year-old study on rhinovirus in adults (JAMA 1967;202;494-500). Surprisingly, it wasn't until earlier this year that good data became available regarding the symptom profile of colds in otherwise healthy school-aged children. In that study, which utilized nasopharyngeal aspirates and symptom diaries, 73% of 81 children with colds continued to be symptomatic 10 days after onset (Pediatr. Infect. Dis. J. 2008;27:8-11).

These new findings suggest we've probably been overtreating a proportion of school-aged children—for bacterial sinusitis—when they actually have had mild to moderate upper respiratory symptoms. Further, these data should provide reassurance that we're not putting such patients at risk for invasive complications if we don't treat before 10 days of illness, as long as they do not fit the acute severe criteria or the symptoms aren't getting rapidly worse.

Data from another recent study suggest that children with acute sinusitis who are destined to develop subperiosteal orbital abscess (SPA) typically do so well before 10 days of rhinorrhea. In this 10-year retrospective chart review from a tertiary pediatric center, 39 children required operative drainage for SPA, with only a mean of 1.6 days of antibiotics prediagnosis in just 10 (26%). Of the 28 children presenting with fever, the mean duration was 2.5 days. Only 28 had rhinorrhea/mucoid discharge, and that for a mean duration of 3.9 days (Int. J. Pediatr. Otorhinolaryngol. 2007;71:1003-6). Thus, complications arose in the first days of symptoms, even among those children on antibiotics.

Since it's not feasible—or wise—to give antibiotics to every child with cold symptoms in order to prevent SPA, the authors concluded that “SPA may not be a preventable complication of acute sinusitis in children” using standard oral antibiotics. Indeed, this paper suggests that children destined to develop complications are by and large not the ones who appear in your office with mild symptoms at days 4 to 7.

If the child has high fever and facial pain or swelling, there's little question you're going to treat. But for those without clear signs of toxicity or rapidly progressing disease, complications seem unlikely after 4 days.

A third study, of pneumococcal mastoiditis complicating acute otitis media (AOM), suggests that severe complications of URIs in children are becoming more difficult to treat with our usual oral drugs because of the emergence of multidrug-resistant pneumococcal serotype 19A, a strain that is not included in the 7-valent pneumococcal conjugate vaccine (PCV7).

Among 41 children with pneumococcal mastoiditis (mean age 23 months, range 3 months-12 years) who were seen at Texas Children's Hospital, Houston, between January 2005 and June 2007, 19 cases were caused by 19A. That strain was responsible for all cases of pneumococcal mastoiditis seen in 2006 and 2007, compared with just three of six seen between 2004 and 2005, and just one of two in 2003 (Pediatrics 2008;122:34-9).

Even more worrisome, all of the children with 19A mastoiditis had SPA, compared with only 2 of the 22 children with non-19A mastoiditis. Mastoidectomy was required in 17 of the 19A group (89%) compared with just 10 (45%) of those with non-19A strains. Thirteen of the 19A isolates (68%) were resistant to all antibiotics tested routinely.

These data correspond to what I've been seeing at my institution. We're seeing less otitis and sinusitis overall since the introduction of PCV7 in 2000. A concern in the last 2-3 years is that the incidence of difficult-to-treat pneumococcal mastoiditis—nearly all due to 19A—has risen among the difficult-to-treat AOM that does occur. In fact, I'm now seeing as much serious invasive pneumococcal disease as before PCV7 was licensed, nearly half due to 19A.

I believe there are two messages here. First, if you withhold antibiotics for 10 days in a nontoxic child with rhinorrhea, according to the guidelines, you probably aren't putting him or her at any greater risk for complicated sinus disease; even treating then is likely to overtreat a proportion of children. Second, we may need a new strategy for persistent or complicated AOM when 19A is the pathogen. These cases may not even respond to clindamycin or three doses of ceftriaxone and may require linezolid or a quinolone (JAMA 2007;298:1772-8) despite the new Food and Drug Administration black box warning on quinolones, usually along with a subspecialty consultation.

But there is hope on the horizon. Wyeth Pharmaceuticals, which partially funded the Texas mastoiditis study, announced at the end of May that the FDA has granted fast-track designation to the company's investigational 13-valent pneumococcal conjugate vaccine for infants and toddlers. That vaccine contains 19A as well as serotypes 1 and 3, the most common causes of empyema.

It's becoming obvious that we will need to stay ahead of the game from now on. Ongoing surveillance will be critical as we move forward.

I have no current disclosures for any products mentioned in this article.

pdnews@elsevier.com

The data from three recent studies should prompt us to reexamine our approach to the management of upper respiratory infections in children.

Guidelines from the American Academy of Pediatrics recommend antimicrobial treatment for children with upper respiratory symptoms lasting longer than 10-14 days or for those with severe symptoms, including a high fever and toxicity (Pediatrics 2001;108:798-808). The Sinus and Allergy Health Partnership Guidelines—to which I contributed—also advised antimicrobial treatment for children with signs and symptoms of viral upper respiratory infection (URI) for more than 10 days or worsening symptoms after 5-7 days (Int. J. Pediatr. Otorhinolaryngol. 2002;63:1-13).

Now data suggest that we perhaps should consider antibiotic treatment only for children whose symptoms are worsening after 10 days.

The recommendation to treat rhinorrhea beyond 10 days with antibiotics as presumptive bacterial sinusitis requires a subjective judgment, and is based on small data sets.

This is problematic in an era in which we're trying to limit antimicrobial use to times when there is definite benefit. It's also been difficult to follow in practice, because parents often bring a child in who has had symptoms for fewer than 10 days. We're not supposed to treat at that point unless they have acute toxicity, but there can be a lot of real or perceived pressure to prescribe.

In fact, the 10-day rule appears to derive from a 40-year-old study on rhinovirus in adults (JAMA 1967;202;494-500). Surprisingly, it wasn't until earlier this year that good data became available regarding the symptom profile of colds in otherwise healthy school-aged children. In that study, which utilized nasopharyngeal aspirates and symptom diaries, 73% of 81 children with colds continued to be symptomatic 10 days after onset (Pediatr. Infect. Dis. J. 2008;27:8-11).

These new findings suggest we've probably been overtreating a proportion of school-aged children—for bacterial sinusitis—when they actually have had mild to moderate upper respiratory symptoms. Further, these data should provide reassurance that we're not putting such patients at risk for invasive complications if we don't treat before 10 days of illness, as long as they do not fit the acute severe criteria or the symptoms aren't getting rapidly worse.

Data from another recent study suggest that children with acute sinusitis who are destined to develop subperiosteal orbital abscess (SPA) typically do so well before 10 days of rhinorrhea. In this 10-year retrospective chart review from a tertiary pediatric center, 39 children required operative drainage for SPA, with only a mean of 1.6 days of antibiotics prediagnosis in just 10 (26%). Of the 28 children presenting with fever, the mean duration was 2.5 days. Only 28 had rhinorrhea/mucoid discharge, and that for a mean duration of 3.9 days (Int. J. Pediatr. Otorhinolaryngol. 2007;71:1003-6). Thus, complications arose in the first days of symptoms, even among those children on antibiotics.

Since it's not feasible—or wise—to give antibiotics to every child with cold symptoms in order to prevent SPA, the authors concluded that “SPA may not be a preventable complication of acute sinusitis in children” using standard oral antibiotics. Indeed, this paper suggests that children destined to develop complications are by and large not the ones who appear in your office with mild symptoms at days 4 to 7.

If the child has high fever and facial pain or swelling, there's little question you're going to treat. But for those without clear signs of toxicity or rapidly progressing disease, complications seem unlikely after 4 days.

A third study, of pneumococcal mastoiditis complicating acute otitis media (AOM), suggests that severe complications of URIs in children are becoming more difficult to treat with our usual oral drugs because of the emergence of multidrug-resistant pneumococcal serotype 19A, a strain that is not included in the 7-valent pneumococcal conjugate vaccine (PCV7).

Among 41 children with pneumococcal mastoiditis (mean age 23 months, range 3 months-12 years) who were seen at Texas Children's Hospital, Houston, between January 2005 and June 2007, 19 cases were caused by 19A. That strain was responsible for all cases of pneumococcal mastoiditis seen in 2006 and 2007, compared with just three of six seen between 2004 and 2005, and just one of two in 2003 (Pediatrics 2008;122:34-9).

Even more worrisome, all of the children with 19A mastoiditis had SPA, compared with only 2 of the 22 children with non-19A mastoiditis. Mastoidectomy was required in 17 of the 19A group (89%) compared with just 10 (45%) of those with non-19A strains. Thirteen of the 19A isolates (68%) were resistant to all antibiotics tested routinely.

These data correspond to what I've been seeing at my institution. We're seeing less otitis and sinusitis overall since the introduction of PCV7 in 2000. A concern in the last 2-3 years is that the incidence of difficult-to-treat pneumococcal mastoiditis—nearly all due to 19A—has risen among the difficult-to-treat AOM that does occur. In fact, I'm now seeing as much serious invasive pneumococcal disease as before PCV7 was licensed, nearly half due to 19A.

I believe there are two messages here. First, if you withhold antibiotics for 10 days in a nontoxic child with rhinorrhea, according to the guidelines, you probably aren't putting him or her at any greater risk for complicated sinus disease; even treating then is likely to overtreat a proportion of children. Second, we may need a new strategy for persistent or complicated AOM when 19A is the pathogen. These cases may not even respond to clindamycin or three doses of ceftriaxone and may require linezolid or a quinolone (JAMA 2007;298:1772-8) despite the new Food and Drug Administration black box warning on quinolones, usually along with a subspecialty consultation.

But there is hope on the horizon. Wyeth Pharmaceuticals, which partially funded the Texas mastoiditis study, announced at the end of May that the FDA has granted fast-track designation to the company's investigational 13-valent pneumococcal conjugate vaccine for infants and toddlers. That vaccine contains 19A as well as serotypes 1 and 3, the most common causes of empyema.

It's becoming obvious that we will need to stay ahead of the game from now on. Ongoing surveillance will be critical as we move forward.

I have no current disclosures for any products mentioned in this article.

pdnews@elsevier.com

The data from three recent studies should prompt us to reexamine our approach to the management of upper respiratory infections in children.

Guidelines from the American Academy of Pediatrics recommend antimicrobial treatment for children with upper respiratory symptoms lasting longer than 10-14 days or for those with severe symptoms, including a high fever and toxicity (Pediatrics 2001;108:798-808). The Sinus and Allergy Health Partnership Guidelines—to which I contributed—also advised antimicrobial treatment for children with signs and symptoms of viral upper respiratory infection (URI) for more than 10 days or worsening symptoms after 5-7 days (Int. J. Pediatr. Otorhinolaryngol. 2002;63:1-13).

Now data suggest that we perhaps should consider antibiotic treatment only for children whose symptoms are worsening after 10 days.

The recommendation to treat rhinorrhea beyond 10 days with antibiotics as presumptive bacterial sinusitis requires a subjective judgment, and is based on small data sets.

This is problematic in an era in which we're trying to limit antimicrobial use to times when there is definite benefit. It's also been difficult to follow in practice, because parents often bring a child in who has had symptoms for fewer than 10 days. We're not supposed to treat at that point unless they have acute toxicity, but there can be a lot of real or perceived pressure to prescribe.

In fact, the 10-day rule appears to derive from a 40-year-old study on rhinovirus in adults (JAMA 1967;202;494-500). Surprisingly, it wasn't until earlier this year that good data became available regarding the symptom profile of colds in otherwise healthy school-aged children. In that study, which utilized nasopharyngeal aspirates and symptom diaries, 73% of 81 children with colds continued to be symptomatic 10 days after onset (Pediatr. Infect. Dis. J. 2008;27:8-11).

These new findings suggest we've probably been overtreating a proportion of school-aged children—for bacterial sinusitis—when they actually have had mild to moderate upper respiratory symptoms. Further, these data should provide reassurance that we're not putting such patients at risk for invasive complications if we don't treat before 10 days of illness, as long as they do not fit the acute severe criteria or the symptoms aren't getting rapidly worse.

Data from another recent study suggest that children with acute sinusitis who are destined to develop subperiosteal orbital abscess (SPA) typically do so well before 10 days of rhinorrhea. In this 10-year retrospective chart review from a tertiary pediatric center, 39 children required operative drainage for SPA, with only a mean of 1.6 days of antibiotics prediagnosis in just 10 (26%). Of the 28 children presenting with fever, the mean duration was 2.5 days. Only 28 had rhinorrhea/mucoid discharge, and that for a mean duration of 3.9 days (Int. J. Pediatr. Otorhinolaryngol. 2007;71:1003-6). Thus, complications arose in the first days of symptoms, even among those children on antibiotics.

Since it's not feasible—or wise—to give antibiotics to every child with cold symptoms in order to prevent SPA, the authors concluded that “SPA may not be a preventable complication of acute sinusitis in children” using standard oral antibiotics. Indeed, this paper suggests that children destined to develop complications are by and large not the ones who appear in your office with mild symptoms at days 4 to 7.

If the child has high fever and facial pain or swelling, there's little question you're going to treat. But for those without clear signs of toxicity or rapidly progressing disease, complications seem unlikely after 4 days.

A third study, of pneumococcal mastoiditis complicating acute otitis media (AOM), suggests that severe complications of URIs in children are becoming more difficult to treat with our usual oral drugs because of the emergence of multidrug-resistant pneumococcal serotype 19A, a strain that is not included in the 7-valent pneumococcal conjugate vaccine (PCV7).

Among 41 children with pneumococcal mastoiditis (mean age 23 months, range 3 months-12 years) who were seen at Texas Children's Hospital, Houston, between January 2005 and June 2007, 19 cases were caused by 19A. That strain was responsible for all cases of pneumococcal mastoiditis seen in 2006 and 2007, compared with just three of six seen between 2004 and 2005, and just one of two in 2003 (Pediatrics 2008;122:34-9).

Even more worrisome, all of the children with 19A mastoiditis had SPA, compared with only 2 of the 22 children with non-19A mastoiditis. Mastoidectomy was required in 17 of the 19A group (89%) compared with just 10 (45%) of those with non-19A strains. Thirteen of the 19A isolates (68%) were resistant to all antibiotics tested routinely.

These data correspond to what I've been seeing at my institution. We're seeing less otitis and sinusitis overall since the introduction of PCV7 in 2000. A concern in the last 2-3 years is that the incidence of difficult-to-treat pneumococcal mastoiditis—nearly all due to 19A—has risen among the difficult-to-treat AOM that does occur. In fact, I'm now seeing as much serious invasive pneumococcal disease as before PCV7 was licensed, nearly half due to 19A.

I believe there are two messages here. First, if you withhold antibiotics for 10 days in a nontoxic child with rhinorrhea, according to the guidelines, you probably aren't putting him or her at any greater risk for complicated sinus disease; even treating then is likely to overtreat a proportion of children. Second, we may need a new strategy for persistent or complicated AOM when 19A is the pathogen. These cases may not even respond to clindamycin or three doses of ceftriaxone and may require linezolid or a quinolone (JAMA 2007;298:1772-8) despite the new Food and Drug Administration black box warning on quinolones, usually along with a subspecialty consultation.

But there is hope on the horizon. Wyeth Pharmaceuticals, which partially funded the Texas mastoiditis study, announced at the end of May that the FDA has granted fast-track designation to the company's investigational 13-valent pneumococcal conjugate vaccine for infants and toddlers. That vaccine contains 19A as well as serotypes 1 and 3, the most common causes of empyema.

It's becoming obvious that we will need to stay ahead of the game from now on. Ongoing surveillance will be critical as we move forward.

I have no current disclosures for any products mentioned in this article.