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One-half of S. pneumoniae infections found in children younger than 2 years

A community-based study of drug-resistant S. pneumoniae, where pneumococcal infections are most prevalent, showed high resistance to newer antibiotics.

[Study findings] [Newer antibiotics]

[Your turn]

November 1998

SAN DIEGO - Children younger than the age of 2 provided one-half of strains of Streptococcus pneumoniae reported in a national study from the University Hospitals of Cleveland and the Hershey Medical Center. Almost 1,500 strains of S. pneumoniae were collected from community-based physicians in 31 states, grouped into six different regions.

"The large number of resistant isolates from children is a significant finding, as is the fact that 25% of all strains were from the middle ear in children," said Michael R. Jacobs, MD, PhD, head of clinical microbiology at University Hospitals of Cleveland and professor at Case Western Reserve University in Cleveland, Ohio.

"Middle ear fluid is not routinely collected from children with otitis media unless an ear tap is performed or the ear drum ruptures, which is not very common," he said. These results show how resistant strains can persist after treatment, because ear taps are usually only performed in cases of treatment failure.

Children were featured predominantly in the study because of the increased disease prevalence and antimicrobial use that occurs at younger ages. "A significant number of strains of bacteria collected were from patients under the age of 2 years, which is the population most likely to have ear infections. Our results indicate the importance of understanding resistance to specific antibiotics," said Jacobs.

Other studies of this kind normally take place in hospital rather than community-based labs. "[The] aim was to determine the current epidemiology of drug-resistant S. pneumoniae (DRSP) in the population where pneumococcal infections are most prevalent, and where most antibiotics are prescribed," he said. Jacobs also noted the need "to see what is happening in the 'real world,' and this is why the results are so different from previous hospital-based studies."

Study findings

Penicillin-Macrolide Cross-Resistance
% Strains by Penicillin Category
Macrolide Category	Susceptible	Intermediate	Resistant
Susceptible	94.9	60.8	32.6
Resistant	5.1	39.2	67.4

Fifty percent of the S. pneumoniae strains were found to be non-susceptible to penicillin. Of those 50%, almost 18% were penicillin-intermediate and 32.5% were penicillin-resistant, with considerable variation by region.

"The terminology penicillin `susceptible, intermediate and resistant' is confusing - what this really means is that intermediate strains require between 10- to 100-fold more b-lactam to have the same effect as the agent would have on fully susceptible strains, while resistant strains require 200- to 1,000-fold more drug to be effective," said Jacobs.

Middle ear and sinus specimens produced the highest resistant strains. The study also found that penicillin-resistance (intermediate and resistant) was highest in children younger than 2 years (58.3%).

The highest S. pneumoniae penicillin-resistance rates were returned from middle ear (58%) and sinus (61%) specimens. Penicillin-resistance rates were high for specimens from the nasopharynx in all age groups. More specifically, the study determined that the group with the highest prevalence of penicillin-intermediate or -resistant S. pneumoniae were children under 2 years of age with otitis media in the Southeast and South Central regions.

The three southern regions studied produced the highest overall penicillin resistance (54% to 62% resistant), while the three northern regions showed the lowest resistance (39% to 51% resistant). Macrolide resistance was also highest in the South Central region (49% resistant) and lowest in the Northern regions (19% to 25% resistant).

"Resistant pneumococci spread by dissemination of a few [five to 10] major resistant clones, which have now spread throughout the world. Presumably such strains were introduced into the South and have spread northwards into the rest of the United States," he said.

Newer antibiotics

Newer antibiotics were less effective in treating strains of S. pneumoniae. About one-third of S. pneumoniae strains showed resistance to antibiotics such as azithromycin (Zithromax, Pfizer), clarithromycin (Biaxin, Abbott), cefprozil (Cefzil, Bristol-Myers Squibb) and cefuroxime (Ceftin, Glaxo Wellcome) and one-half to cefixime (Suprax, Wyeth-Lederle). Accurate diagnosis is needed to stem the levels of resistance shown by these newer antibiotics. "The results suggest the need to reevaluate the use of newer, broad-spectrum antibiotics against these common bacteria," said Jacobs.

"The newer oral cephalosporins are essentially only reliably active against penicillin-susceptible strains, which account for slightly less than 50% of strains," he said.

These antibiotics are more broad-spectrum and are not as necessary when managing common bacterial respiratory infections, which can be treated with more active drugs such as amoxicillin or amoxicillin/clavulanate. Respiratory infections caused by viruses should not be treated with antimicrobials.

"Amoxicillin, one of the oldest b-lactams, is the most active b-lactam against current strains of pneumococci. Amoxicillin-clavulanate has the same activity as amoxicillin against pneumococci, but is the best agent for empiric use in otitis media, sinusitis, etc., when b-lactam-producing organisms (Haemophilus influenzae and Moraxella catarrhalis need to be covered," he said.

Further studies are needed to guide community use of antimicrobials when treating S. pneumoniae. "Currently, over 100 million prescriptions are written for antibiotics in the United States each year by community physicians, with 75% being for respiratory tract infections [especially otitis media]," said Jacobs.

For your information:

• Jacobs M, Bajksouzian S, Lin G, Applebaum P. Variation in antimicrobial resistance of community isolates of Streptococcus pneumoniae by age, region and disease. Presented at the 38th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Sept 24-27. San Diego.

Your turn

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Copyright 2000, SLACK Incorporated. Revised 15 September 2000.