Pediatric Infectious Disease Journal:
ANTIBIOTIC SCRIPTS FOR CHILDREN The most frequently asked questions to our infectious disease consultation team deal with selection of appropriate antibiotic therapy, both for hospitalized and ambulatory children in Dallas, TX. The recent creation of the Antibiotic Stewardship Committee (ASC) at Children’s Medical Center Dallas has helped to define the use of antibiotics in different areas of the hospital and clinics and to educate physicians, especially residents, on selection of appropriate agents for therapy of specific infections. The overuse of antibiotic in pediatrics was recently illustrated by several publications. For example, Chai and associates (Pediatrics 2012; 130:23) from the Center for Drug Evaluation and Research of the US Food and Drug Administration assessed the frequency and patterns of national ambulatory drug utilization using large prescription databases. Overall, 263.6 million prescriptions were written in 2010 for pediatric patients up to 18 years of age, of which approximately one-quarter was for antimicrobials. This represents a total reduction of 7% in scripts written from 2002 and for antibiotics specifically, a reduction of 14%. For 0-23 month olds 5 of the 10 top drugs dispensed to pediatric patients were antimicrobials with amoxicillin and azithromycin leading the list. These two antibiotics led the list for 2-11 year olds as well. In a study from the European Union, Grossman and colleagues (Acta Paediatrica DOI: 10.1111/j.1651-2227.2012. 02754.x) conducted a survey of pediatricians and participants of the European Academy of Paediatrics Research in Ambulatory Setting Network on attitudes of antibiotic prescribing for upper respiratory infections. Greater than 40% of respondents overestimated the risks of not prescribing antibiotics and the clinical benefits of antibiotic therapy for otitis media and tonsillitis. Clearly education of physicians everywhere is needed to impact prescribing habits. For example, Michael Smith and coworkers from Kosair Children’s Hospital, Louiseville, KY (Pediatrics 2012; 129:e1326–e1333) reviewed their use of parenteral antibiotics for community acquired pneumonia in infants and children. Records for 1246 patients were reviewed. Guidelines emphasizing use of ampicillin for empiric therapy were developed in 2007-2008 by their ASC. Ampicillin use increased 44% from before to after release of their guidelines and conversely, use of ceftriaxone decreased 28% after guideline publication. These data emphasize the importance of guidelines and education. Finally, prescribing patterns for management of urinary tract infections in children were reviewed using data from the National Ambulatory Medical Care and National Hospital Ambulatory Medical Care Surveys (Pediatrics 2011; 127;1027). Trimethoprim-sulfamethoxazole, considered appropriate initial therapy, was prescribed in 52% of children from 1998 to 2000 and in 47% from 2005-2007. There was no overall increased use in broad spectrum antimicrobials (e.g. amoxicillin-clavulanate, quinolones, macrolides and first and second generation cephalosporins) with the exception of parentally and orally administered third generation cephalosporins. The latter drugs were prescribed more frequently for those less than 2 years of age, females and when temperature was greater than 100.4 °F. Despite admonitions to the contrary, antibiotics continue to be over prescribed despite recommendations from ASCs and organizations such as the American Academy of Pediatrics. Will it ever change?
STUDENT VERSUS MENTOR Selman Waksman is acclaimed as the discoverer of streptomycin and was awarded the Nobel Prize for that achievement. Streptomycin is mostly a historic footnote because it is little used now, but in 1943, when it was discovered, it was big news. It was not only effective against many Gram-negative bacteria, but it was the first antibiotic active against the tubercle bacillus. The actual discovery of streptomycin was made by Albert Schatz, a graduate student of Dr. Waksman at Rutgers College of Agriculture. Dr. Waksman’s role was to arrange with people at the Mayo Clinic to test streptomycin in guinea pigs and then in humans. Dr. Waksman got the glory and a great deal of money in royalties. Dr. Schatz got the scorn of the academic community for having the effrontery to sue his professor for recognition of his discovery. Schatz appealed to the Nobel Committee, which ruled that he was a mere laboratory assistant to an eminent scientist. This story is recounted in a new book by Peter Pringle, “Experiment Eleven: Dark Secrets Behind the Discovery of a Wonder Drug” (Published by Walker & Company). The author found the long-lost laboratory records of Dr. Schatz confirming that Schatz made the discovery independent of Waksman. He should have at least shared the Nobel Prize. Both men are long dead so only historic accuracy would be served by giving Schatz his due reward. There is probably a lesson in this story for Research Fellows, but we will not go there.
MALARIA LABORATORY STUDIES We saw a memo from Dr. Paul Arguin of the CDC Malaria Branch offering malaria species confirmation and drug resistance testing for cases of malaria diagnosed and treated in the United States. There is no charge for this service. Local diagnosis of malaria should be based on microscopy or an antigen detection test. For instructions about shipping of the blood sample see http://www.cdc.gov/malaria/features/ars.html At the CDC they will do PCR confirmation of species, identify drug resistance mutations and attempt parasite culture for susceptibility testing. Dr. Arguin says that they would like to have samples from every case in the U. S., so don’t be shy about contacting them when you encounter a case of malaria.
RAW MILK AND REAL MILK In the faculty parking garage we saw a bumper sticker on a car (a hybrid) that proclaimed “Raw Milk Heals”. It did not specify what it heals - diseases, wounds, broken hearts, what? Beneath that statement in smaller letters was www.realmilk.com. We decided to check the website and found that “this website recommends Real Milk-that is, milk that is full-fat, unprocessed, and from pasture-fed animals. Nor do we recommend consumption of lowfat or skim raw milk - there are important protective factors in the butterfat. Real Milk contains many antimicrobial and immune-supporting components.” The words “Real Milk” are capitalized so we assume that is a trade name for milk that is obtained and stored under clean conditions at a commercial site. We could not find at the website a listing of the “many antimicrobial and immune-supporting” substances found in Real Milk but not in pasteurized milk. It was interesting to us that a member of a medical school faculty is promoting the healing powers of raw milk. He or she must feel that they outweigh the well-documented risk of infection from raw milk.
THE BODY’S MICROBIAL GARDEN The New York Times, our favorite lay source of medical information, had an interesting article on June 18, 2012 about recent information on the human microbiome project. Featured within the article were two studies concerning the microbiomes of pregnant women and breast milk. Dr. Kjersti Aagaard and her colleagues from Baylor College of Medicine, Houston, TX (PLoS ONE 7(6): e36466) described the microbiome of 24 healthy pregnant women from 18 to 40 weeks gestational age and compared results with those from 301 non-pregnant controls. To their surprise the overall diversity and richness of the vaginal bacteria reduced dramatically during the first trimester. Lactobacilli dominated during pregnancy and in particular, Lactobacillus johnsonii proliferated. This organism is usually located in the gut and is known to produce enzymes that digest milk. Because the baby will be colonized with this organism after birth, Dr. Aagaard speculated that the inoculum assists the infant in digesting milk. In a second featured article, Dr. Katherine Hunt and colleagues (PLoS ONE 6(6): e21313) investigated the microbiome of breast milk samples obtained from 16 women at different times. The bacterial communities were complex and breast milk had up to 600 species of bacteria with several genera often predominating and these were generally stable in each individual. Additionally, the milk contained oligosaccharides that serve to nourish certain beneficial bacteria in the infant’s intestine.