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Clinicians continue to call for more data on CAP guidelines
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It was just more than a year ago that the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America released their long-awaited guidelines on the diagnosis and treatment of community-acquired pneumonia. Data are just starting to emerge on how these guidelines may affect practice.
Although study results published just last month showed that the availability of community-acquired pneumonia (CAP) guidelines in hospitals had a negligible effect on resource utilization, they also showed that these guidelines can influence patterns of antimicrobial use.
This research, along with other studies about antibiotic use for CAP, has been a central topic of discussion at many recent infectious diseases meetings. A common theme emerged from all of these discussions; specifically, that the publication of the CAP guidelines will undoubtedly help to standardize the approach to the care of the child with pneumonia.
Guideline overview
The 52-page joint guidelines recommended immunizations as the best way to protect children from severe pneumonia and called for preventing bacterial pneumonia as the top priority, according to
Kaplan cited data that showed nearly a 55% reduction in invasive pneumococcal disease since introduction of the 7-valent pneumococcal conjugate vaccine (Prevnar, Pfizer), and he said many experts are anxiously awaiting data on the 13-valent pneumococcal conjugate vaccine (Prevnar13, Pfizer) regarding pneumonia.
Kaplan, a member of the Infectious Diseases in Children Editorial Board, said the guidelines are separated into several categories, including management decisions; diagnostic testing for pediatric CAP; anti-infective treatment; adjunctive surgical and non–anti-infective therapy for pediatric CAP; management of the child not responding to treatment; discharge criteria; and prevention.
Sheldon L. Kaplan, MD, from Texas Children’s Hospital, said clinical judgment is essential to diagnose CAP in children.
Photo courtesy of Lampp L
For each of the 92 recommendations in the guidelines, the authors denote the strength of the recommendation, as well as the quality of evidence for each. The guidelines also indicate a lack of evidence in some areas, which is often a result of the ethical challenges of studying children, and urge research in specific areas, he said.
“The guidelines are helpful,” Kaplan said. “But I don’t think they give you everything you need to know all the time. You have to use your best clinical judgment.”
The guidelines define Streptococcus pneumoniae as the most common bacterial pathogen and the best target for empiric therapy, according to Kaplan.
“Viruses play major roles in younger children,” he said, citing data from Dallas Children’s Medical Center that indicated of all children hospitalized with pneumonia, 23% had the presence of both bacterial and viral infections.
Testing for CAP
The PIDS/IDSA guidelines recommend that infants aged 3 to 6 months with suspected bacterial pneumonia would likely benefit from hospitalization, even if pneumonia is not confirmed by blood tests. Blood testing in children does not always reveal the cause of pneumonia; therefore, physicians should closely evaluate the patient’s symptoms and err on the side of treating if unsure, according to Kaplan.
“Blood cultures should not be routinely performed in nontoxic, fully immune children with CAP managed in the outpatient setting,” he said. “But blood cultures should be obtained in those children who fail to demonstrate clinical improvement and in those who show clinical deterioration even after antibiotics.”
Shah wrote a paper in 2011 that evaluated blood cultures for children with pneumonia. The paper concluded: “Children presenting to the ED for evaluation of CAP are at low-risk for bacteremia. Although positive blood cultures frequently altered clinical management, the overall impact was small because of the low prevalence of bacteremia.”
In the outpatient setting, “blood cultures infrequently identify pathogens, in fewer than 2% of cases, and false positives are common,” Shah said, adding that results of these cultures rarely influence treatment decisions in the outpatient setting.
However, blood cultures are more helpful in the inpatient setting, particularly with empyemas.
“If you don’t obtain a blood culture, you may not be able to make a microbiologic diagnosis, and sometimes that helps in narrowing therapy choices,” he said.
The guidelines recommended pulse oximetry in outpatient settings, and the panel’s recommendations on chest X-rays were “one of the most controversial in the document,” Shah said, because they should not be routinely recommended in outpatient settings.
The rationale for that recommendation, according to Shah, was that “chest X-rays do not reliably distinguish bacterial from viral CAP, and … they are often impractical in the office setting. Additionally, there may be barriers to pediatricians obtaining the results in a time frame to guide decision making.”
Other tests for pneumonia can be conducted with sputum and urinary samples. However, Kaplan said sputum samples are sometimes difficult to obtain and urinary tests are not recommended in children because of a high rate of false positives.
The guidelines call for rapid tests during certain seasons to evaluate children with CAP because “antimicrobial therapy will not routinely be required for these children in the absence of laboratory or radiographic findings that suggest a coinfection,” Kaplan said, adding that these tests have their shortcomings.
During her presentation, Dennehy said an algorithm for rapid viral testing should be considered because they have proved helpful with other diseases. For example, clinicians who suspect influenza may want to consider testing in outbreak situations, patients in intensive care, and those children who are at an elevated risk of complications from respiratory illnesses.
CAP treatment
Regarding treatment of CAP, the guidelines have several recommendations.
Shah presented the guidelines’ algorithm for CAP treatment, which recommended “treatment for the shortest effective duration will minimize exposure of both pathogens and normal microbiota, and minimize the selection for resistance.”
Shah said this recommendation was qualified as strong, but with a low quality of evidence.
“Treatment courses of 10 days have been best studied,” he said.
The guidelines also recommended that shorter courses may be as effective, particularly for more mild disease managed on an outpatient basis, which Shah said was a strong recommendation with moderate quality of evidence.
For infections caused by certain pathogens, notably community-associated methicillin-resistant Staphylococcus aureus, the CAP guidelines state that longer treatment may be required compared with infections caused by S. pneumoniae. Shah said this recommendation was also qualified as a strong recommendation with moderate-quality evidence.
High-dose oral amoxicillin at 90 mg/kg per day covers 87% to 95% of S. pneumoniae isolates, whereas most second- and third-generation oral cephalosporins cover only 60% to 70%, Kaplan said.
Azithromycin is not recommended for suspected pneumococcal CAP, he said.
Guideline shortcomings
The outpatient treatment portion of the guidelines is an area where some practitioners, including Infectious Diseases in Children Editorial Board member
Block said the guidelines “ignored a lot of data on atypical pathogens.” For most CAP in preschoolers, pediatricians typically attempt to decide whether to treat in the outpatient setting for atypical “bacteria” of “walking pneumonia” or the rare (<3% of blood cultures) S. pneumoniae, which has in the past always been associated with high fever, high leukocyte counts and more ill appearance.
However, the guidelines have taken the position that routine antimicrobial therapy is not routinely required for preschool-aged children with CAP because viral pathogens are the most common cause of pneumonia in this age group.
While the guidelines recommend amoxicillin as first-line therapy, and macrolides are an appropriate option if there is a high suspicion for pneumonia caused by atypical bacteria such as Mycoplasma, Block disagreed with these recommendations. He cited three studies related to ambulatory CAP in the United States, which he said indicate that both amoxicillin-clavulanate and either of the macrolides (azithromycin or clarithromycin) have been highly effective and without any risk of increased complications in children with mild ambulatory CAP, which is a common condition. The macrolides may have a distinct advantage (at least in vitro) over amoxicillin if the two atypical pathogens are the dominant bacteria in CAP after routine use of PCV13, said Block, who has been in private practice for more than 30 years and is also professor of clinical pediatrics at the University of Kentucky College of Medicine and the University of Louisville Medical School.
“Actually, previous data have documented the detection of atypical bacteria more commonly than viral pathogens in outpatients with radiographically and clinically proved CAP,” he said.
Azithromycin for 5 days has a shorter course and easier dosing than clarithromycin or amoxicillin (with or without clavulanate) for 10 days, according to Block. However, there are concerns about resistance with azithromycin, he said.
Guidelines in practice
“Personally, I like the guidelines. There is work that needs to be done to improve the evidence around a lot of the recommendations, certainly, and the issue of whether or not the guidelines get followed is a much bigger issue,” Neuman said.
Neuman and colleagues published a study recently that assessed the relationship between institutional clinical practice guidelines and care utilization, antibiotic administration and outcomes among children who had CAP and were admitted to hospitals with their own institutional-based practice guidelines for CAP.
In the study, researchers sent surveys to the quality officer at each participating hospital to establish whether the institution had a clinical practice guideline for the treatment of children with CAP. Hospitals that responded positively to the questionnaire regarding an institutional clinical practice guideline were asked to share them.
Guidelines from each institution were reviewed for information related to diagnostic testing and antimicrobial selection. The researchers compared overall and specific utilization patterns, antimicrobial use and hospital length of stay for children with CAP between hospitals with and without clinical practice guidelines.
According to the study, 13 of 41 hospitals had an institutional clinical practice guideline for non-severe CAP. Among the 19,710 children hospitalized with CAP, costs of care, hospital length of stay and 14-day readmission rates were not associated with the presence of a clinical practice guideline.
Penicillin or aminopenicillins were prescribed to 46.3% of children at institutions where a clinical practice guideline had recommended the use of these antibiotics as first-line agents, compared with 23.9% of children at institutions without a clinical practice guideline (OR=2.7; 95% CI, 1.4-5.5).
In addition, the study indicated that the existence of guidelines did not influence ordering patterns for most diagnostic tests, such as chest radiographs and blood cultures.
Neuman and colleagues concluded from the study that the local guidelines influenced antibiotic selection in each of the hospitals, but did not seem to influence the performance of diagnostic testing.
“This is a complicated issue,” Neuman said. “These guidelines [from PIDS/IDSA] will serve as a basis for institutions to develop their own guidelines, or to modify their own local guidelines. More importantly, the study demonstrates the need for institutions to monitor whether their guidelines are being followed on the local level.”
He also said their study noted “substantial variability” between institutions for each diagnostic test. As an example, six hospitals recommended blood culture, four did not. The same was true for viral testing.
“One of the main reasons for the variability in the care of children with pneumonia relates to the lack of a gold standard to establish the diagnosis,” Neuman said. “Unlike most other infections, like urinary tract infection, for instance, we rarely know the etiologic agent responsible for the pneumonia, which makes it tougher for these recommendations to be universally followed. But my hope is they will lead to more standardization of local practices an improve care for children with pneumonia.”
X-rays unnecessary for outpatients
Although X-rays are commonly performed when pneumonia is suspected in patients seen in the ED, the PIDS/IDSA guidelines now recommend against performing a chest X-ray in patients with non-severe pneumonia treated in the outpatient setting, which Neuman said may be challenging for ED clinicians.
“As an ED doctor, there’s a lot of difficulties involved in not getting a chest X-ray; mainly, that our clinical exam findings are not always accurate for defining pneumonia. Clinicians tend to overestimate the likelihood of pneumonia based on physical examination findings alone. By not performing chest X-rays, it may actually lead to increased use of antibiotics,” he said.
Kaplan said more data are needed on many aspects of the guidelines, adding that he is hopeful that CDC’s Evaluation of Processes and Indicators in Infection Control (EPIC) study, which is currently under way, may help with that data. In addition, the EPIC study will likely provide further insight into viruses such as human metapneumovirus, respiratory syncytial virus and pneumococcal disease and their role in CAP onset and treatment. – by Colleen Zacharyczuk
References:
Block S. Pediatr Infect Dis J. 1995;14:471-477.
Bradley JS. Clin Infect Dis. 2011;53:e25-76.
Feigin RD. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. 6th ed. Philadelphia, Pa.: Saunders Elsevier; 2011.
Harris JA. Pediatr Infect Dis J. 1998;17:865-871.
Musher DM. Clin Infect Dis. 2001;32:534-538.
Neuman MI. Pediatrics. 2012;130:e823-830.
Wubbel L. Pediatr Infect Dis J. 1999;18:98-104.
For more information:
Sheldon L. Kaplan, MD, can be reached at skaplan@bcm.edu.
Mark I. Neuman, MD, MPH, can be reached at Boston Children’s Hospital, Division of Emergency Medicine, 300 Longwood Ave., Boston, MA 02115; Email: mark.neuman@childrens.harvard.edu.
Samir S. Shah, MD, MSCE, can be reached at samir.shah@cchmc.org.
Disclosure: Dennehy, Kaplan, Neuman and Shah report no relevant financial disclosures.