The infinite trio from South Africa

Last week I had the pleasure of attending the 8th FIDSSA Congress in Johannesburg (Federation of Infectious Diseases Societies of Southern Africa). I was invited to talk on infection control in the Netherlands, SDD and empiric antibiotic strategies in ICU. I never felt more distance between my habitat and that of my hosts. It surpassed the 3732 miles in the air. I learned a lot; from how it is to go into military conflict areas to identify Ebola cases, fighting a cholera outbreak after a tropical cyclone in Mozambique to the infinite trio, which stands for carbapenem resistant Klebsiella, Pseudomonas and Acinetobacter.

The current status in (probably many) hospitals in South-Africa is that of endemicity of this infinite trio. I heard proportions as high as 40% of carbapenem resistance among clinical isolates. In one centre the risk of untreatable infections after stem cell transplantation had reached such levels that I asked at what point they would decide no longer to perform that treatment. “I think we are close to that point”, was the answer. Michelle Lowe gave an excellent overview of the molecular epidemiology of that outbreak, or actually of the tip of the iceberg. The 1st OXA-48 carrier was detected in 2011 in a patient that came from Egypt. Since then the number of CPE rose in their private hospital with an exponential increase in 2015-6. They analysed 574 isolates (all clinical, no screening) and most Klebsiella pneumoniae isolates were ST307 harbouring OXA-181 CTX M15 and an identical plasmid, forming a distinct genetic clade (clade VI). This strain emerged in 2013 and was – within 15 months – detected in 350 patients in 42 private hospitals in 23 cities (see Eurosurv April 2019). Infection control measures were used, but failed, at least partly due to persistent environmental contamination, despite fogging and the other works.

I also learned about new antibiotic combinations, such as colistin + ertapenem + meropenem, and that Ceftazidime-Avibactam has reached the status of the ultimate life-saver. Yet, it seems difficult to get the antibiotic and the costs are high (although nobody could tell me the exact price for 1 week of treatment). I’m afraid that currently the price is the only mechanism against widespread use, selection and transmission of bacteria resistant to Ceftazidime-Avibactam. Another colleague told me that in his hospital recently legs from three patients were amputated because of prosthetic joint infections with carbapenem-resistant Acinetobacter. One woman with an infected hip prosthesis eventually died. Acinetobacter PJI? Well, Acinetobacter and Klebsiella (mostly carbapenem resistant) are the most prevalent causes of bloodstream infection in one of the largest neonatal ICUs in the country. I trust these babies were not born with these bacteria.

I also learned about the different healthcare systems; 85% is public sector and 15% is private. They both spend an equal amount on healthcare. In the private sector the physician has a contract with the patient and rents space in the hospital to see patients. That physician earns his/her income on procedures and prescriptions (including antibiotics) and he/she (and the hospital) have no incentive to spend a Rand on infection control and antibiotic stewardship. As a proof of concept: in such hospitals 80% of births are planned (i,e,. Caesarean sections), I heard from a colleague whose wife is a midwife. Moreover, patients shop freely in the private sector, where previous culture results are not shared between hospitals or labs, and where screening is considered wasteful spending. Not surprisingly, resistance problems are more prominent in the private sector. The OXA-181 outbreak also is in private hospitals. There is a Dutch word for such apart systems, that I just can’t remember.

So, this short visit into the fields of antibiotic resistance confirmed many of my (previously expressed) expectations for the future of AMR. Antibiotic resistance will be the next plague in the lower and middle income countries, where new antibiotics (if any) will not be affordable and with a healthcare system that is not prepared to respond appropriately. I learned that a national Healthcare Program should replace private hospitals in the next 10 years. But even if successful, that might be too late. The sober stats of the Ebola outbreak in Congo on Nov 7th (3286 cases, 2190 death) impress and alert the world. Yet, an even larger epidemic is breeding.

Fortunately, I also heard very positive things. One night, I had dinner with four clinical microbiologists and after the opening chitchat about rugby, I asked if anyone knew a Dutch clinical microbiologist that once practiced in Durban, Wim Sturm. Well, that was a nice opening. Two of them were trained by him, and spoke very warmly about his teaching (“always packed lecture halls”) and his charm. It looked as if they still had a crush on him, and both ladies admitted that they (at least) had had it once. Apparently, Wim Sturm educated many highly motivated and qualified clinical microbiologists in South Africa.

And for patients: HIV treatment has really progressed in this part of the world, and there is great progress in treating MDR-TB, with cure rates above 90%. How come? Huge fundings from NGOs and large investments from big pharma in new treatments. The same will be needed for the next epidemic.

Looking back on a very pleasant, informative and inspirational visit in a country that  has many things to be proud of, not just their Springbokken.

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