Daniel M. Keller, PhD

September 27, 2011

September 27, 2011 (Chicago, Illinois) — Bacteria like to get down and dirty, swapping genes in the sewage effluent from hospitals. This makes it possible for multidrug-resistant strains to be generated with resistance specific to drugs commonly used in a particular hospital, researchers warn.

Here at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, senior author Ana Gales, MD, PhD, professor of medicine in the division of infectious disease at the Universidade Federal de São Paulo, Brazil, presented evidence of the Klebsiella pneumoniae carbapenemase (KPC) gene in nosocomial pathogens and in environmental bacteria present in hospital sewage.

The KPC gene, initially found in K pneumoniae (hence the designation), was within transposons carried by plasmids in diverse bacterial genera, indicating its potential to transfer and spread across a wide range of hosts.

Dr. Ana Gales

KPC can inactivate all β-lactam antibiotics, Dr. Gales said. Its spread, therefore, jeopardizes the ability to prescribe many antibiotics to treat infections.

No law in Brazil requires the treatment of hospital effluent before it is released into the public sewage system. Dr. Gales explained that contact between clinical pathogens and environmental bacteria, with selective pressure from broad-spectrum antimicrobials, is perfect for the exchange and spread of resistance genes.

The investigators collected samples of sewage from a large university hospital; cultured, isolated, and reisolated bacteria; and then identified isolates using matrix-assisted laser desorption/ionization – time-of-flight mass spectrometry, with the genus confirmed by 16S recombinant DNA sequencing for all KPC producers. Antimicrobial susceptibility was determined with standard disc diffusion and agar dilution methods. KPC-encoding genes were searched for by amplification, using polymerase chain reactions, and then by doing Southern blots, using a probe specific for the bla KPC-2 gene.

A total of 130 Gram-negative bacteria types were recovered from the sewage, of which 21 carried the KPC-encoding gene. The majority of isolates were Enterobacter, Citrobacter, Kluyvera, and Raoultella species. Bacterial mating assays were successful for all isolates, indicating that the gene was carried on plasmids.

For the first time, KPC was identified in Aeromonas and Kluyvera species, considered to be predominantly environmental bacteria. No clinical isolates of these bacteria producing KPC were recovered by the microbiology laboratory during the study period, suggesting that the bacteria had picked up the KPC-encoding gene in the hospital's sewage. The investigators therefore concluded that these species could act as opportunistic pathogens or resistance reservoirs that might accelerate antimicrobial resistance in the community.

"We don't know...if these isolates will survive carrying the resistance genes in the environment or not," Dr. Gales told Medscape Medical News. She plans a second phase of the study to sample water in reservoirs after it has been through the community sewage treatment process.

She hesitates to make any recommendations on the basis of the study's findings. "For most individuals, it will not make any difference, but for immunocompromised patients or for special situations, maybe," she said.

As an example of what can happen when certain genes get together, she cited a recent outbreak of disease in Germany caused by Escherichia coli. "The problem is the environment, and [bacteria] are exchanging information. The E coli in Germany have 2 different mechanisms of virulence that were together in 1 isolate," Dr. Gales said.

Jesús Rodriguez-Baño, MD, PhD, head of infectious diseases at University Hospital Macarena in Seville, Spain, told Medscape Medical News that he found the study "absolutely interesting because there are many obscure areas in the epidemiology of resistance genes and the reservoirs that we don't understand very well."

Because patients who are admitted to a hospital are at high risk of harboring resistant bacteria, he said, the study is an important step in gaining insight into how bacteria and genes behave in other environments.

"This is like looking at one point of the whole epidemiological channel," Dr. Rodriguez-Baño pointed out. "It will also be very important to see if the resistance genes that are isolated in the sewage are the same as those that are endemic or epidemic within a single area hospital, so that we can have the whole picture of the epidemiology."

Seeing how resistance genes get into the hospital and into epidemic clones from bacteria outside the hospital, and how spread within the hospital environment influences what happens outside of it, "is a new way of looking at this epidemiological relationship between genes," he said.

The study received no commercial support. Dr. Gales reports being a consultant to Pfizer and Novartis, but said these relationships are not relevant to this study. Dr. Rodriguez-Baño has disclosed no relevant financial relationships.

51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract C2-669. Presented September 18, 2011.