The Arms Race We Are Losing: Antimicrobial Resistance and What Every Clinician Can Still Do

Aseel H. AlZibdeh, MD, MPH
Transplant Infectious Diseases Specialist, Hamad Medical Corporation
Assistant Professor of Clinical Medicine, Weill Cornell Medicine

Every specialty is running on borrowed time

In 2019, infections resistant to antibiotics killed at least 1.27 million people and were associated with nearly 5 million deaths. That is more than HIV or malaria (1).

Every hip replacement, every cycle of chemotherapy, every transplant depends on an antibiotic working when it is needed. In our region, roughly one in three common bacterial infections no longer responds to standard treatment (2). The drugs are not failing at some point in the future. They are failing now, on wards we work in.

World Antimicrobial Awareness Week runs from 18 to 24 November. This article is about three things: how bacteria defeat our drugs, how few drugs are left, and what a clinician in any specialty can do about it this month.

How bacteria win

A bacterium divides every twenty minutes. A new antibiotic takes ten to fifteen years (3). That is the whole contest in two sentences.

Bacteria do not need to invent a single clever trick. They have five, and they combine them (4).  

The part that should alarm every prescriber is this: resistance genes travel. A plasmid carrying a carbapenemase can move from one species to another in a patient who has never received a carbapenem (4). Your patient can inherit resistance from someone else’s prescription.

In the Eastern Mediterranean, about one in three common bacterial infections is already resistant (5). Among bloodstream isolates worldwide, 44.8% of E.coli and 55.2% of K. pneumoniae resist third-generation cephalosporins. Resistance rose in more than 40% of the bug-drug pairs monitored between 2018 and 2023 (5).

The last drugs are already cracking

When a cephalosporin fails, we reach for a carbapenem. When a carbapenem fails, we reach for a handful of newer combinations or for colistin, a drug abandoned in the 1970s for its toxicity (6). There is no shelf behind that one.

·       Carbapenems. Resistance reached 54.3% in Acinetobacter bloodstream infections worldwide. In South-East Asia, carbapenem-resistant K. pneumoniae bacteremia hit 41.2% (5).

·       Ceftazidime-avibactam. Approved in 2015 as the answer to KPC-producing Klebsiella. Resistant variants appeared after 9 to 18 days of treatment in some patients, through single amino-acid changes in the KPC enzyme (7).

·       Resistance without exposure. KPC-8 Klebsiella resistant to ceftazidime-avibactam has caused primary infection in a patient never treated with the drug (8).

These are not laboratory curiosities. They are what happens in a hospital where the last-line drug is used often enough. Use is what creates the variant.

The pipeline is a trickle

The World Health Organization (WHO) counted the antibacterial agents in clinical development in February 2025. There were 90, down from 97 in 2023. Only 15 qualified as innovative. Only 5 of those agents act against at least one of the WHO’s critical priority pathogens (9) .

Since 2017, 17 new antibacterials have reached the market. Two represent a new chemical class. The rest are variations on molecules bacteria have already learned to defeat (9).

Meanwhile, new drugs do not pay. Merck has withdrawn imipenem-relebactam from the US market, citing a portfolio review rather than any safety or quality problem (10). Commentators point to the underlying economics: a drug held in reserve, used only when nothing else works, sits on the shelf and earns little (10). The drugs we most need to preserve are the ones the market least wants to make.

The arithmetic is plain. Resistance climbs 5% to 15% a year in nearly half the pairs we track. Innovation delivers a new class once a decade. We cannot invent our way out faster than bacteria evolve. What we can control is how fast we burn what we have.

Qatar has set its course. The second National Antimicrobial Resistance Action Plan (2024-2030), launched in November 2024, follows a One Health approach with objectives for stewardship, surveillance, infection prevention, and professional education (11). A plan changes nothing until it reaches the prescribing decision on the ward. That is where the rest of this article goes.

Four questions, asked before the results

Every antibiotic order is a bet. Four questions turn it from a guess into a decision. None are complicated. Each one protects the patient in front of you and the drug for the next one.

1. Is it infection, and is it bacterial? Name the syndrome and the source. Send cultures before the first dose. Most antibiotic errors begin with an infection that was assumed and never confirmed.
2. Which drug, and does it fit the local pattern? Start with the antibiotic that covers the likely pathogens for this site. The WHO AWaRe book sets out Access agents first, Watch and Reserve agents for documented or high-risk resistance (12).
3. Can it be narrowed at 48 to 72 hours? Culture results, clinical response, and source control should trigger a formal review. Write down the decision either way.
4. When does it stop? Put a stop date in the order. In the BALANCE trial, 7 days of antibiotics was non-inferior to 14 days for bloodstream infections with no increase in 90-day mortality. (Caveat: the study excluded severely immunosuppressed patients, deep seated infections and S. aureus bacteremia)(13).

Sunday morning, one change at a time

No new system is needed to start. Each item below fits into a ward round that already happens.

Pick two. Do them this week.

• Write the stop date on every order. The date forces the review that the order would otherwise skip.
• Send cultures before the first dose when the patient can safely wait for them. Cultures are the only thing that turns a guess into evidence.
• Read the local antibiogram before choosing empiric therapy. Note the date it was compiled. An antibiogram from two years ago describes a different hospital.
• Review every Watch and Reserve agent at 48-72 hours. Document the decision, whichever way it goes.
• Step down to oral therapy where the patient can take it and the infection allows it.
• Explain why antibiotics do not treat viral illness. Patients who leave understanding the reason ask for fewer prescriptions next time.

The next patient

Bacteria will keep evolving. The pipeline will keep trickling. Neither of those is in our hands. What is in our hands is the rate at which we spend the drugs that still work. A stop date on an order, a culture sent before the first dose, a Watch agent narrowed at 72 hours: each one buys time for a drug that nobody is going to replace.

This World Antimicrobial Awareness Week, choose one change on your ward and make it routine.

References:

1. Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022 Feb;399(10325):629–55. doi:10.1016/S0140-6736(21)02724-0

2. World Health Organization. Antimicrobial resistance [fact sheet]. [Internet]. Geneva: World Health Organization; 2026. Available from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

3. World Health Organization. 2021 Antibacterial Agents in Clinical and Preclinical Development: An Overview and Analysis. 1st ed. Geneva: World Health Organization; 2022.

4. Communicable Disease Center. About Antimicrobial Resistance [Internet]. 2025 Jan 31. Available from: https://www.cdc.gov/antimicrobial-resistance/about/index.html

5. Organization WH. Global Antibiotic Resistance Surveillance Report 2025: WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS). 1st ed. Geneva: World Health Organization; 2025.

6. Nation RL, Li J. Colistin in the 21st century: Curr Opin Infect Dis. 2009 Dec;22(6):535–43. doi:10.1097/QCO.0b013e328332e672

7. Shi Q, Han R, Guo Y, Yang Y, Wu S, Ding L, et al. Multiple Novel Ceftazidime-Avibactam-Resistant Variants of bla_KPC-2 -Positive Klebsiella pneumoniae in Two Patients. Hockett KL, editor. Microbiol Spectr. 2022 Jun 29;10(3):e01714-21. doi:10.1128/spectrum.01714-21

8. Mateo-Vargas MA, Rodríguez-Pallares S, Arca-Suárez J, López-Cerero L, Rodríguez-Iglesias M, Galán-Sánchez F. Emergence of KPC-8-producing K. pneumoniae infection without prior exposure to ceftazidime/avibactam: the threat of de novo infections by ceftazidime/avibactam-resistant KPC variants. Carattoli A, editor. Antimicrob Agents Chemother. 2025 Jun 4;69(6):e01494-24. doi:10.1128/aac.01494-24

9. World Health Organization. WHO releases new reports on new tests and treatments in development for bacterial infections [Internet]. 2025 Oct 2. Available from: https://www.who.int/news/item/02-10-2025-who-releases-new-reports-on-new-tests-and-treatments-in-development-for-bacterial-infections

10. Chris Dall. Merck pulls antibiotic for multidrug-resistant infections from US market [Internet]. 2026 Sep 30. Available from: https://www.cidrap.umn.edu/antimicrobial-stewardship/merck-pulls-antibiotic-multidrug-resistant-infections-us-market

11. Qatar News Agency. MoPH Launches Second Qatar National Antimicrobial Resistance Action Plan 2024-2030 [Internet]. 2024 Nov. Available from: https://qna.org.qa/en/news/news-details?date=4%2F11%2F2024&id=0055-moph-launches-second-qatar-national-antimicrobial-resistance-action-plan-2024-2030

12. The WHO AWaRe (Access, Watch, Reserve) Antibiotic Book. 1st ed. Geneva: World Health Organization; 2022. 1 p.

13. The BALANCE Investigators. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med. 2025 Mar 13;392(11):1065–78. doi:10.1056/NEJMoa2404991