This article is more than 5 years old. Information may no longer be current.
Finally, pediatric CAP guidelines unveiled
Click Here to Manage Email Alerts
The recently published pediatric community-acquired pneumonia guidelines from the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America are long overdue. They were thoughtfully formulated by a consensus group of some of the best, most august and respected pediatric ID specialists in the United States. The approach to the patient with pneumonia is superbly crafted … and extremely thorough.
Lacking anything else to critique, I would only quibble with a few areas in outpatient management of community-acquired pneumonia (CAP) from a generalist pediatrician point of view.
First, although it may seem obvious, I would like to have seen which actual physical examination findings are thought to comprise the diagnosis of pneumonia in the US office. I would venture to say that 95% or more of all CAP we diagnose in practice are “walking pneumonia,” a mild to moderate form, which is usually diagnosed by presence of pulmonary rales. Wheezing is often concomitantly present and does not exclude CAP, as we have published in The Pediatric Infectious Disease Journal in 1995.
As the guidelines state, rarely is chest radiograph deemed necessary in these cases. However, the role of high fever and/or high white blood cell count heavily influences our decision whether to hospitalize or empirically use intramuscular ceftriaxone. Occasionally, in general practice, more moderate to severe CAP cases (needing chest X-ray and parenteral antibiotics) are associated with decreased breath sounds, pleuritic pain, chest splinting or high fever/leukocytosis.
Second, the etiology and treatment of pneumonia in the 3- to 5-year-old age group is perhaps presented as the glass is “half empty,” as far as atypical pathogens and prescribing macrolides. For most CAP in preschoolers, we are usually trying to decide whether we should empirically treat for atypical pathogens (the common walking pneumonia) or Streptococcus pneumoniae (the rare sicker-looking pneumonia, or rarely Staphylococcus aureus or respiratory syncytial virus [RSV]/influenza, etc). However, the guidelines have taken the position that “routine antimicrobial therapy is not routinely required for preschool-aged children with CAP because viral pathogens account for the great majority of disease.”
Studies from the 1990s
Two large multicenter US national studies in 1998 and 1995 by Harris (n=420) and Block (n=260), respectively, assessed and treated outpatient radiographically proven CAP in non-toxic children (aged 5 years and younger and aged 3 to 4 years: n=197 and n=90, respectively). Using imperfect methods for culture/polymerase chain reaction and titers, Chlamydia pneumoniae was detected in 9% and 23% of children, respectively, and Mycoplasma pneumoniae was detected in 15% and 23% of children, respectively. Thus, 24% to 45% of preschoolers had atypical pathogens detected, depending on how many children aged younger than 2 years were enrolled.
The role of S. pneumoniae in non-bacteremic pneumonia in the CAP guidelines in children aged 3 to 5 years (detected in approximately 20% to 28%) was based on a twofold rise in anti-pneumolysin and other S. pneumoniae titers over 2 to 5 weeks from multiple smaller studies. Children aged younger than 24 months and/or hospitalized sicker children comprised almost half of studied children aged younger than 5 years who had positive titers (up to 28%) detected in some studies. Arguably, S. pneumoniae titers have been shown to be specific for S. pneumoniae disease in some studies, and as non-specific in other pediatric and adult studies.
Yet, S. pneumoniae titer rises are often documented in new-onset pneumococcal acute otitis media or even nasopharyngeal colonization — which may occur frequently or simultaneously in this younger age group. Only three blood cultures were positive for S. pneumoniae in all three US studies analyzing more than 300 children aged younger than 5 years with outpatient CAP.
The US studies on CAP were also conducted in the mid-1990s, before the universal immunization with pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth), which has reduced the rates of S. pneumoniae invasive disease by more than 95%. PCV7 and PCV13 (Prevnar13, Wyeth) will also likely have additional major effect upon current rates of proposed non-bacteremic CAP caused by S. pneumoniae, even of mild severity.
As for the treatment of ambulatory CAP in the three US studies, it seems that both amoxicillin-clavulanate and either of the macrolides (azithromycin or clarithromycin) have been comparably highly effective in children with commonly encountered, mild ambulatory CAP — also without any risk of increased complications. The macrolides may have a distinct advantage (at least in vitro) currently over amoxicillin if the two atypical pathogens are the dominant bacteria in CAP after routine use of PCV13. Azithromycin for 5 days has a shorter course and easier dosing than clarithromycin or amoxicillin (with or without clavulanate) for 10 days. There are concerns about increasing S. pneumoniae resistance when using azithromycin.
Dilemmas with ‘non-treatment’
Considering “non-treatment” of toddlers and preschoolers with CAP leaves the practitioner with some dilemmas when explaining to parents. The earnest clinical and medicolegal discussion and office time needed will be quite challenging: “Your 2- or 3-year-old child has mild pneumonia. We are not going to treat him because the majority of the time it is supposed to be viral. However, actual evidence/data before PCV13 says that he has a 1 in 4 chance of a potentially bad bacteria (S. pneumoniae), and possibly a 40% or greater chance of a lower grade treatable bacteria. We have firm evidence that 90% to 95% of the time a child will get better in a week or so when treated with certain antibiotics. But, we have no data on how the child with known CAP comparatively fares without antibiotics; or if they have higher rates of complications. They will probably do fine, I think.”
Often, during the next 1 to 2 days, they will then go to the urgent care center or competitor for the persistent cough and get the antibiotic that “those doctors should have prescribed.” Realistically, we still get continual parental complaints about not treating the upper respiratory infection, much less pneumonia.
As for the outpatient management of the infrequently encountered child with CAP plus leukocytosis or high fever, or more ill-appearing, or with lobar pneumonia, I still prefer to use one to three daily doses of intramuscular ceftriaxone over the use of amoxicillin, and particularly azithromycin (minimal evidence for the drugs here). This child is much more worrisome for having S. pneumoniae CAP and early invasive disease, despite the fact that only about 5% of these children will have a positive blood culture in pediatric offices, as was noted in the guidelines. Strains of S. pneumoniae with penicillin resistance, which respond readily to ceftriaxone’s much higher serum levels, still linger as well.
Ignoring my nitpicking, we should heartily thank the authors of the guidelines for their massive, incredibly diligent work on this heretofore neglected area.
Congratulations.
For more information:
- Block S. Pediatr Infect Dis J. 1995;14:471-477.
- Bradley JS. Clin Infect Dis. 2011;doi:10.1093/cid/cir531.
- Feigin RD. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. 6th Edition. Philadelphia, Pa.: Saunders Elsevier; 2011.
- Harris JA. Pediatr Infect Dis J. 1998;17:865-871.
- Musher DM. Clin Infect Dis. 2001;32:534-538.
- Wubbel L. Pediatr Infect Dis J. 1999;18:98-104.
Dr. Block is a general pediatrician in private practice in Bardstown, Ky., and is a member of the Infectious Diseases in Children Editorial Board. Disclosure: Dr. Block serves as a consultant for Pfizer on PCV13.
Dr. Block has done a superb job of pointing out several of the areas for which we need much better data on the diagnosis and management of CAP in children. The published studies, which represent the “scientific evidence” for our assessments and recommendations, are often lacking in scope and scientific rigor (many cited by Dr. Block), which is why so many of the recommendations are associated with evidence that is less than “high quality.”
However, when published data were lacking, we resorted to the “expert opinion” of both the writing group members and the societies that provided these collaborators for this project. The group assembled for this task was not just pediatric infectious disease specialists (who represented about one-third of the entire group), but was deliberately composed of all who are involved in the care of these children, including Dr. Swanson from Ames, Iowa, who, like Dr. Block, is a “generalist pediatrician.”
The diverse pediatric specialists who wrote and reviewed this document included those in hospitalist medicine, pulmonology, surgery, emergency medicine, critical care medicine and an epidemiologist physician from the CDC. We were acutely aware of all the issues raised by Dr. Block, and even included a 19-item table that identified priority areas for future investigation. Hopefully, this table will generate both research protocols and funding.
To directly address a few of Dr. Block’s concerns, I wish to emphasize that these are just guidelines, recognizing that clinical judgment is still essential to providing excellent care to children. We have defined the reasons why, for the first time in decades, clinicians can choose ampicillin or amoxicillin to treat pneumonia, rather than more broad-spectrum therapy with ceftriaxone (although intramuscular ceftriaxone continues to be a unique way to provide short-term outpatient parenteral therapy).
Consensus exists that high rates of usage of antibiotics (particularly more broad-spectrum antibiotics, and those that have prolonged exposure characteristics, like azithromycin) will result in increased antibiotic resistance, not only in the treated child, but also in the community. We are giving Dr. Block and colleagues the opportunity now to consider not routinely using antibiotics to treat each child with rales on exam, most of whom will have viral pneumonia (which the parents may better understand as a “chest cold” and not demand antibiotic therapy). We were emphatic in highlighting the need for better point-of-care diagnostic techniques, so Drs. Block and Swanson, from their offices, can determine whether the child has a viral chest cold or bacterial pneumonia. Those tests currently do not exist.
We also provide information on an area that remains confusing and requires much better understanding: how certain viral lower respiratory tract infections (like influenza) can increase the susceptibility to bacterial pneumonia that will require antimicrobial therapy.
Most of the preschool children with CAP have viral disease when sophisticated molecular techniques are used. These children will, of course, appear to the parents (and physicians) to respond to antimicrobial therapy when prescribed, as the children will usually improve within 48 to 72 hours.
Unfortunately, most of the clinical trials testing new antimicrobials for children, to allow FDA approval and marketing, have not done a good job of identifying pathogens, as we cannot ethically perform invasive procedures such as bronchoscopy just to obtain an accurate microbiologic diagnosis. But by enrolling into these studies all children with fever, cough and chest radiograph changes (“radiographically proven”), now realizing that most will actually have viral pneumonia, all drugs appear to work well (very similar to our situation with otitis media studies in which a red ear and fever allowed enrollment).
To address Dr. Block’s concerns for Mycoplasma pneumoniae, we cite a recent publication on levofloxacin (which is active against both the usual respiratory bacteria, as well as M. pneumoniae) vs. amoxicillin/clavulanate, for CAP, that evaluated pneumonia outcomes in the subgroup of children between 6 months and 5 years of age. Much to our surprise, in this prospective, randomized study, the levofloxacin and amoxicillin/clavulanate cure rates were similar for M. pneumoniae (around 80% to 90%) at the test-of-cure visit, despite that amoxicillin/clavulanate is not believed to have any activity against M. pneumoniae. So it seems that Dr. Block may not need to worry about azithromycin therapy for M. pneumoniae in preschool children, as diagnosed and evaluated in this large, 700-patient, multicenter, multi-country clinical trial.
In summary, we learned that the quality of most of the scientific evidence to support our management of children with CAP is poor. However, we must accept and embrace the challenge to perform the required studies and improve outcomes in pediatric CAP, realizing that these guidelines are just the first step.
Thank you, Dr. Block.
– John S. Bradley, MD
University of California at San Diego and Rady Children’s Hospital
Disclosure: Dr. Bradley reports no relevant financial disclosures.
 |
Follow the PediatricSuperSite.com on Twitter. |