By Meryl Nass, M.D.
‘Non-vaccine Strep serotype 19A, which is multidrug resistant, spread throughout the world as the result of the niche created by vaccination with the 7-serotype vaccine … The strains of Strep pneumoniae circulating among us have changed as a result of the Prevnar vaccine, and the new strains are decidedly more drug resistant. I’d rate this vaccine’s net value a big negative … the serious unintended consequence of Prevnar (the 19A proliferation) needs to be fully grasped, and the lesson absorbed, in order to avoid making a similar mess with other vaccines.
By Meryl Nass, M.D. April 24, 2012
I have treated so many patients with sinusitis in the last several weeks, I decided to review new guidelines that were issued by the Infectious Diseases Society of America (IDSA) recently on sinusitis. Wow, the changes were BIG and I had missed them. Seems the drugs I used to use don’t work so well any more.
Everyone has heard about drug resistance. We had to watch a movie about it in medical school in the 1970s. It was very important that we not use antibiotics with broader, more powerful antimicrobial effects than necessary. Else plagues of drug-resistant bacteria would rain down upon us, and we would run out of effective antibiotics.
I got it. Use basic, relatively narrow spectrum antibiotics unless there is a very good reason to use the bigger guns — like your patient was so sick he might not survive if you picked the wrong drug to start.
Plus, there are very few new antibiotics in the pipeline.
I recently learned that 80% of the antibiotics sold in the US don’t treat humans. These antibiotics are used in animal feed, enabling owners of livestock and poultry farms to crowd the animals together, where they frequently live in their own merde. Although FDA banned this use of fluoroquinolone antibiotics in 2005, compliance by industry has been poor. (Industry can still feed the animals other classes of antibiotics.) So FDA will now restrict sales of this class of antibiotic to only those with a veterinarian’s prescription, and ask farmers for voluntary compliance in reducing use of other antibiotics, 61 years after first approving this practice.
Yale’s Dr. David Katz notes that the use of antibiotics in farm animals is a bigger problem for drug resistance than doctors choosing the wrong antibiotics.
Back to my patients with sinusitis: too many of them needed a change in antibiotic after 4 days on the first antibiotic. Good drugs for sinusitis used to include penicillins, cephalosporins, macrolides and sulfa drugs. That’s four different categories of drugs. Now they are inadequate, caused by too many resistant Strep. pneumoniae and Hemophilus influenzae, the most common bacteria causing sinusitis.
What now? IDSA’s #1 choice is Augmentin, a very broad spectrum combination of amoxicillin and clavulanic acid. The clavulanic acid prevents most bacterial resistance to amoxicillin. This treatment may cause more drug resistance down the road.
But what if you are allergic to penicillin? Doxycycline or a fluoroquinolone can be used. Doxy can’t be used in children, however. What else should you use? Clindamycin and a cephalosporin, say the guidelines. But Clostridium difficile infections occur in 1-10% of patients treated with clindamycin. These can be impossible to treat. This is not looking good, I realize.
Then it gets worse. What has happened? IDSA let the cat out of the bag on page e16:
… both the prevalence of H. influenzae (40%– 45%) and proportion of b-lactamase–producing H. influenzae (37%–50%) (extrapolated from middle ear fluid cultures of children with acute otitis media) have markedly increased among other upper respiratory tract infections since the widespread use of conjugated pneumococcal vaccines…
Whereas S. pneumoniae was more common than H. influenzae prior to 2000, the prevalence of H. influenzae has clearly increased while that of S. pneumoniae has decreased in the post–pneumococcal vaccine era, such that currently they are approximately equal… (* See IDSA citation below)
Now 30% of Strep pneumoniae are resistant to macrolides, while 30-40% are resistant to sulfa drugs (page e3). What IDSA didn’t delve into was the fact that non-vaccine Strep serotype 19A, which is multidrug resistant, spread throughout the world as the result of the niche created by vaccination with the 7-serotype vaccine. Recently a replacement pneumococcal conjugate vaccine was licensed that includes 23 serotypes. Any unintended consequences have yet to be identified.
The strains of Strep pneumoniae circulating among us have changed as a result of the Prevnar vaccine, and the new strains are decidedly more drug resistant. I’d rate this vaccine’s net value a big negative.
Yet the consequences of this change in resistance patterns is profound. Now routine cases of sinusitis, earaches, strep throats and pneumonias have become significantly harder and more expensive to treat. I can’t tell you the relative contributions that Prevnar vaccine, prescribing errors and antibiotic feeding make to this mess. But the serious unintended consequence of Prevnar (the 19A proliferation) needs to be fully grasped, and the lesson absorbed, in order to avoid making a similar mess with other vaccines.
* Casey JR, Adlowitz DG, Pichichero ME. New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr Infect
Dis J 2010; 29:304–9.
Impact of pneumococcal conjugate vaccine on infections caused by antibiotic-resistant Streptococcus pneumoniae.
Pediatric Infectious Disease Unit, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. firstname.lastname@example.org
Studies have shown that vaccination with seven-valent pneumococcal conjugate vaccine (PCV7) results in a decline in nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae, in carriage of vaccine-type pneumococci, and in replacement by non-vaccine serotypes. Vaccines can reduce pneumococcal resistance in vaccinated and unvaccinated populations by reducing the carriage of antibiotic-resistant serotypes, which protects the vaccinated population and prevents spread of disease to others, and by decreasing antibiotic resistance through overall reduction in antibiotic use. However, while reducing the level of vaccine serotypes and drug-resistant serotypes in the nasopharynx, PCV7 also causes non-vaccine pneumococci replacement. The impact of serotype replacement on disease is not clearly understood. Pelton et al. surveyed two communities shortly after the introduction of the PCV7 immunization programme and found that while colonization with vaccine serotypes declined from 22% to 2% from 2000 to 2003, prevalence of non-vaccine serotypes increased from 7% to 16%. Although penicillin-resistant colonizing S. pneumoniae isolates initially declined, penicillin-intermediate isolates increased 2 years following PCV7 introduction. The change was primarily accounted for by an increase in penicillin-intermediate serotype 19A. Serotype 19A is the only serotype not affected by PCV7 that is prevalent worldwide, clinically important, and highly multidrug-resistant. A study by Hicks et al. established serotype 19A as the predominant post-PCV7 cause of invasive pneumococcal disease (IPD) in children and the elderly. An increase in IPD rates caused by antibiotic-resistant serotype 19A isolates can also occur without vaccination; reports indicate increases in regions characterized by extensive antibiotic use, underscoring the importance of strategies to contain antibiotic resistance.
- [PubMed – indexed for MEDLINE]
- Read the study