Nothing we've seen thus far suggests China is dealing with a `novel' pathogen, but there are persistent reports in China's state run media of high levels of macrolide resistant pneumonia, particularly in young children.
In a (translated) report today from Chinanews.com - Azithromycin resistance rate is high, experts: Reasonable drug use includes drug selection, dosage, and use time - Yu Yunsong, deputy director of Zhejiang Provincial People’s Hospital and infectious disease specialist, was quoted as saying:
"High resistance to azithromycin has always existed in all countries. In most parts of our country, the resistance rate of Mycoplasma pneumoniae isolated from pediatric patients to azithromycin is 60%-90%, while the resistance rate to doxycycline and minocycline is below 5%.”
“The main reason is infection in children. There are fewer drugs available for Mycoplasma pneumoniae, and the most commonly used one is azithromycin. Mycoplasma pneumoniae is naturally resistant to antibiotics that act on cell wall synthesis, such as penicillins and cephalosporins, and the instructions for doxycycline indicate that it is suitable for children over 8 years old. Quinolones such as levofloxacin and moxifloxacin are contraindicated in people under the age of 18."
While resistance to azithromycin can be found in other countries, calling it high in `all countries' is a bit misleading. Resistance is most prevalent in Asia - running as high as 90% in parts of China - with rates in the United States estimated at roughly 10%, and even lower in much of Europe (see chart below).
Credit: The molecular characteristics, diagnosis, and treatment of macrolide-resistant Mycoplasma pneumoniae in children Frontiers in Peds. March 2023
We've also monitored upticks this fall in pediatric pneumonia outside of China (see Denmark SSI Declares A Mycoplasma Pneumonia Epidemic), with the ECDC reporting at least 6 EU/EEA countries seeing increased M. pneumoniae activity, as well as the United States (see CDC NCIRD: Pediatric Pneumonia Update).
But reassuringly, in early December the ECDC reported `There are currently no reports of atypical strains or evidence of resistance to first-line macrolide antibiotics.'
Non-prescription antibiotic dispensing (NPAD) was made illegal in China in 2004, but it remains common practice (cite Determinants of non-prescription antibiotic dispensing in Chinese community pharmacies), with many pharmacies willing to skirt the law.
China's antibiotic crisis has been brewing for years (see 2019's Crisis of Antimicrobial Resistance in China: Now and the Future by Junyan Qu, Yimei Huang, and Xiaoju Lv), often involving serious pathogens such as carbapenem-resistant Acinetobacter, Pseudomonas aeruginosa and Klebsiella pneumoniae.
Among `irrational use' of antibiotics (especially in children and agriculture) listed in the above study, the authors cite:.
- Some general practitioners or rural doctors are unfamiliar with the principles and methods for the rational application of antimicrobials, they may wrongly prescribe antimicrobials in the ways such as incorrect dosing, topical application of systemic antimicrobials, and improper antimicrobial prophylaxis, etc.
- Most often, patients with viral infections (flu or common cold) may be prescribed antimicrobials. A study from Poland also showed increased antimicrobial consumption in viral infection season (Ciszewski et al., 2017).
- Financial incentives, such as mark-ups on drug price, is considered to be the main driver of over-prescribing in China (Qiao et al., 2018).
- Many people have low literacy about antimicrobials, and they pursue antimicrobials through a pharmacy without prescription (online or on site) (Wang et al., 2016).
- Antimicrobials are widely used in livestock as prophylactic and therapeutic agent for infections and as growth promoters. Antimicrobial use in livestock is even slightly higher than in humans (Zhang et al., 2015).
- Antimicrobials have contaminated the food and drinking water supply in China because a large number of antimicrobials are used improperly in livestock in rural China (Hao et al., 2015).
- In 2015, a survey on the antimicrobial body burden of Chinese schoolchildren found that 58.3% of 1064 urine samples were tested positive for antimicrobials, and that the contaminated environment and food may be the main sources of exposure (Wang et al., 2015). This may have induced bacterial resistance and unbalanced flora distribution, damaged the immune function and nervous system, and produced other adverse drug reactions.
In the mid-2000s Amantadine - an influenza antiviral in wide use since the 1960s - abruptly lost its effectiveness. While the Chinese government vigorously denied the allegation, many blamed its inclusion as a prophylactic against bird flu in chicken feed in Asia (see BMJ Use of antiviral drug in poultry is blamed for drug resistant strains of avian flu).
Although the Mycoplasma pneumonia epidemic in China is currently getting a lot of attention, it is a symptom of a much larger problem; the continued erosion of the world's armamentarium against bacterial, viral, and fungal infections.
As we've discussed often (see here, here, and here), every year we draw a little closer to an oft-predicted `post-antibiotic era', where something as simple as a scraped knee, community acquired pneumonia (CAP), or elective surgery, could prove deadly.
In the 2019 report, the last year comprehensive healthcare and community data were available to calculate, CDC estimated that more than 2.8 million antimicrobial-resistant infections occur in the U.S. each year, with more than 35,000 people dying as a result.
The prolonged COVID pandemic proved to be a setback for the fight against antimicrobial resistance in the United States (see below), and presumably many other places in the world.
Short of seeing another COVID or 1918-like pandemic, the biggest threat to global health over the next decade or two is undoubtedly antimicrobial resistance. A few, of many, past blogs include:
AJIC: The impact of the COVID-19 Pandemic on Hospital-Acquired Infections
UKHSA: Gonorrhoea and Syphilis at Record Levels in 2022
Massachusetts DPH: First Detection Of Gonorrhea Strain With Resistance To 5 Classes of Antibiotics
The Lancet: Candida auris - An Emerging Antimicrobial-resistant Organism with the Highest Level of Concern
CDC HAN (Advisory): Outbreak of Extensively Drug-resistant Pseudomonas aeruginosa Associated with Artificial Tears
While I cover AMR topics occasionally in this blog, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about the growing global threat of AMR.
