Nearly 150 serious infections that failed to respond to antibiotics occurred per day last year in England - with experts warning "we are already seeing resistance emerge" to even the newest drugs.
Infections caused by antibiotic-resistant bacteria are "killing thousands" in the UK every year and is not a problem "we can ignore", health officials said.
Figures from the UK Health Security Agency (UKHSA) showed there was an average of 148 severe antibiotic-resistant infections per day in 2021, up by 2.2% on the previous pandemic year (53,985, up from 52,842).
Overall infection numbers were still down on pre-pandemic levels, but the UKHSA said this was driven by things such as reduced social mixing and extra handwashing.
The use of antibiotics - which help fuel antimicrobial resistance (AMR) - also fell by 15% between 2017 and 2021.
AMR occurs when bacteria, viruses, fungi and parasites mutate and no longer respond to the medicines - including antibiotics - that are designed to treat them.
This makes the illnesses very hard to treat and increases the risk of diseases spreading, causing severe illness and death.
Antibiotic resistance occurs naturally, but the overuse of antibiotics can speed up the process.
Professor Dame Jenny Harries, chief executive of the UKHSA, said: "Antibiotic resistance is not a distant problem that we can ignore.
"Infections caused by antibiotic-resistant bacteria are killing thousands of people every year in this country and globally, as well as having a huge economic impact.
"As we emerge from the COVID-19 pandemic, this is a pivotal moment to maintain focus on the 'silent pandemic' of antibiotic resistance."
Professor Susan Hopkins, chief medical adviser at the UKHSA, said: "We are already seeing resistance emerge to our very newest antibiotics - innovation to find new treatments will only succeed if we use what we have responsibly.
"Overuse of antibiotics will mean they stop working against life-threatening conditions such as sepsis.
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"Antibiotics won't help the symptoms of cold, flu or COVID-19 - please trust your healthcare professional, take antibiotics only as prescribed, never share with others and don't save for later.
"Taking antibiotics when you don't need them puts you and your loved ones at risk of having an untreatable infection in future."