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Gram-negative bacteria are a group of bacteria that can cause infections in different parts of the body, including the lungs, urinary tract, wounds and bloodstream. They include common hospital pathogens such as Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. These bacteria can be particularly difficult to treat when they develop resistance to antibiotics. One important group of antibiotics used for serious infections is carbapenems. When these bacteria become resistant to carbapenems, doctors have fewer effective medicines available to treat patients.

The researchers, part of the Indian Council of Medical Research’s antimicrobial resistance surveillance network, looked at four major Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. They compared patients in tertiary hospitals infected with carbapenem-resistant bacteria with those infected by susceptible strains of the same bacteria.

Studying these infections is important because antibiotic resistance can affect both patient survival and the cost of treatment. While many studies monitor how resistant bacteria are in laboratory samples, fewer studies look at what happens to the patients who actually have these infections. This study therefore provides important information on whether resistant infections are linked to higher deaths, longer hospital stays and greater antibiotic costs across different hospitals in India.

The study, conducted across 20 tertiary-care hospitals between April 2022 and April 2025, analysed data from 159,336 hospitalised patients. Of these, 26,213 had confirmed gram-negative bacterial infections, and 16,025 — or 61.1% — had infections resistant to carbapenem antibiotics.

The difference in mortality was seen across all four bacteria. Among patients with E. coli infections, 24.4% of those with carbapenem-resistant infections died, compared with 17.3% among those with susceptible infections. For K. pneumoniae, mortality was 31.2% in the resistant group versus 23.5% in the susceptible group.

The gap was 37.9% versus 32.8% for A. baumannii, and 28.9% versus 20.2% for P. aeruginosa. In relative terms, patients with carbapenem-resistant E. coli had a 41% higher risk of death than those with susceptible E. coli. The corresponding increase was 33% for K. pneumoniae, 16% for A. baumannii and 43% for P. aeruginosa.

The researchers also calculated population attributable fractions for mortality. These ranged from 11.1% for A. baumannii to 18.7% for P. aeruginosa.

However, the authors caution that these estimates should not be interpreted as the exact number of deaths that could be prevented by eliminating resistance because the analysis could not fully account for factors such as severity of illness, timing of appropriate treatment and other clinical variables.

The situation was even more serious when the infection had entered the bloodstream. Among bloodstream infections, mortality among patients with carbapenem-resistant bacteria ranged from 39.3% for E. coli to 50.8% for A. baumannii. For K. pneumoniae, mortality was 44.8%, while it was 46.4% for P. aeruginosa.

In comparison, mortality among patients with susceptible bloodstream infections was 23.8% for E. coli, 36% for K. pneumoniae, 42.6% for A. baumannii and 32.8% for P. aeruginosa.

More than 85% of bloodstream infections across the four bacteria were classified as healthcare-associated, highlighting the importance of infection prevention and control in hospitals.

The study found that antibiotic treatment was more expensive when the bacteria were resistant to carbapenems. For E. coli, the average antibiotic cost was approximately ₹39,846 per patient for resistant infections, compared with ₹20,034 for susceptible infections. For K. pneumoniae, the corresponding figures were ₹55,688 and ₹47,918, respectively. For A. baumannii, treatment costs were approximately ₹62,150 for resistant infections compared with ₹41,372 for susceptible infections, while treatment for P. aeruginosa cost approximately ₹66,599 for resistant infections compared with ₹48,392 for susceptible infections.

Overall, the researchers found that antibiotic treatment costs for carbapenem-resistant infections were about 1.1 to two times higher than for susceptible infections. They point out, however, that these figures include only antibiotic costs and do not include hospital beds, diagnostic tests, doctors’ fees or supportive care. The costs were calculated using national rates for antibiotics available under the government’s JanAushadhi scheme, which are generally lower than market prices. This means the actual financial burden could be higher.

Carbapenems are important antibiotics used to treat serious bacterial infections. When bacteria become resistant to them, doctors have fewer effective treatment options. The study found that newer antibiotics such as ceftazidime-avibactam were used more frequently than polymyxin-based treatment for carbapenem-resistant E. coli and K. pneumoniae. In bloodstream infections caused by these bacteria, ceftazidime-avibactam was associated with lower mortality than polymyxin B.

But the researchers caution against interpreting these findings as proof that one drug is universally better than another. The study did not have patient-level information on several factors that can strongly influence outcomes, including how sick the patient was, how quickly appropriate treatment was started, the source of infection and the specific resistance mechanism.

The majority of infections involving the four bacteria were healthcare-associated: 85% of E. coli, 91.6% of K. pneumoniae, 95.1% of A. baumannii and 91.9% of P. aeruginosa infections fell into this category.

The researchers also found that factors such as the presence of a luminal medical device and recent surgery were more common among patients with resistant infections. This makes infection prevention particularly important, the authors say. Alongside better infection-control practices, hospitals need timely diagnostics so that doctors can identify resistant bacteria and select appropriate antibiotics rather than relying unnecessarily on broad-spectrum drugs.

The message from the study is straightforward: When common hospital bacteria become resistant to carbapenem antibiotics, patients face a higher risk of death and treatment becomes more expensive. The researchers therefore call for stronger antimicrobial stewardship, better infection prevention and control, faster and more accurate diagnostics, and improved access to effective treatments.

They also warn that the study was conducted largely in tertiary hospitals that manage referred and critically ill patients. Therefore, its mortality rates should not be treated as a measure of hospital performance. The authors say outcomes in hospitals with limited laboratory support could potentially be even worse.