Efforts to save mare with life-threatening pneumonia described by researchers

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"Our study highlights how the 'one dominant clone' concept is not an absolute in severe infection."
File image by Joseph Keil

Five co-existing multidrug-resistant isolates of the bacterium Klebsiella pneumoniae were identified in a mare affected by pneumonia following surgery.

K. pneumoniae is a common resident of the healthy mammalian gut, but it is also a leading cause of opportunistic, often severe, infections elsewhere, including sepsis and meningitis.

Multidrug-resistant K. pneumoniae can cause life-threatening illnesses in both animals and humans, with several multidrug-resistant clones causing disease outbreaks worldwide.

“It is generally accepted that only one clone will be dominant in an infection episode,” Carola Venturini and her fellow researchers reported in the journal Microbiology Spectrum.

“In this study, we investigated K. pneumoniae isolates from a horse with severe pneumonia and demonstrated co-occurrence of multiple sequence types previously identified as emerging human pathogens.”

The Australian study team said the equine isolates were not significantly different from one another in terms of virulence or resistance, with equal potential to prolong the duration and severity of infection. They were, they said, indistinguishable from isolates recovered from humans, except for plasmid content.

“Our study highlights how the ‘one dominant clone’ concept is not an absolute in severe infection,” the study team wrote.

Their work, they said, highlights the need for improved diagnostics to track the diverse nature of infections. Further, it reinforces the importance of cross-monitoring of environmental and human reservoirs of multidrug-resistant pathogens.

The case involved a pregnant 12-year-old 600kg mare, who was admitted with severe colic to the Camden Equine Centre at the Sydney School of Veterinary Science, part of the University of Sydney.

A colon torsion was treated by exploratory laparotomy. Care followed standard protocols, including antibiotic therapy with intramuscular penicillin and intravenous gentamicin for the first three days.

Four days after surgery, the mare developed a respiratory infection, characterized by fever, rapid breathing, and mild respiratory distress. The penicillin/gentamicin therapy was replaced with oral trimethoprim-sulfamethoxazole and nebulization with ipratropium bromide and budesonide.

Tracheal fluid was sampled and cultured overnight, with K. pneumoniae confirmed as the primary cause.

After a brief improvement, the mare’s breathing worsened. Oral trimethoprim-sulfamethoxazole treatment was stopped, and silver nebulization was started in addition to continued ipratropium bromide and budesonide therapy.

A second fluid specimen was collected for analysis on day nine, which confirmed continuing infection with K. pneumoniae.

The following day, last-line amikacin treatment was started using a nebulizer. The new therapy resulted in a slow improvement over two weeks, and a third test on tracheal fluid on day 24 confirmed that the infection had been cleared.

The amikacin was discontinued and the mare discharged from hospital on day 25. A low-grade, asthma-like residual respiratory inflammation was present at discharge, but was successfully treated to full recovery with corticosteroids (oral prednisolone and clenbuterol) and bronchodilators at home.

Further analysis, which included molecular-based testing, cast further light on the nature of the mare’s infection. It led to the identification of five coexisting multidrug-resistant K. pneumoniae isolates sharing the same niche.

One was a novel sequence type (ST4656), while the other four were all members of emerging human pathogenic clonal groups (ST307, ST628, ST893 and ST392). All had an equal potential to prolong the length and severity of infection when sharing the same niche, they said.

Discussing their findings, the authors said the origin of the multidrug-resistant strains could not be definitively established as Klebsiella were not isolated from environmental samples tested for routine infection control at the clinic, and no feed or fecal samples – often Klebsiella reservoirs and a likely alternative source – were analyzed.

“It is not uncommon, even in human settings, for the detection of the origin of the infecting Klebsiella to be rather problematic, as this is a ubiquitous, adaptable and widely distributed environmental species.”

They said rapid identification and characterization of antibiotic resistance in infecting strains becomes crucial in ensuring effective treatment and avoiding exacerbation of disease by inappropriate antibiotic choice.

“This study highlights the value of careful screening strategies and smart antibiotic choices for successful therapy, suggesting that testing of multiple colonies from diagnostic specimens should be more routine and that re-introduction of phage typing as an additional screening method, particularly in settings where whole genome sequencing costs cannot be met, could be beneficial.”

The study team comprised Venturini, Bethany Bowring, Sally Partridge, Nouri Ben Zakour, Alicia Fajardo-Lubian, Ariana Lopez Ayala, Jilong Qin, Makrina Totsika, Gaby van Galen, Jacqueline Norris, and Jonathan Iredella, variously affiliated with the Centre for Infectious Diseases and Microbiology, part of the Westmead Institute for Medical Research in New South Wales; the Sydney School of Veterinary Science; Westmead Hospital; and the Centre for Immunology and Infection Control, part of the School of Biomedical Sciences at the Queensland University of Technology.

Co-Occurrence of Multidrug Resistant Klebsiella pneumoniae Pathogenic Clones of Human Relevance in an Equine Pneumonia Case
Carola Venturini, Bethany Bowring, Sally R. Partridge, Nouri L. Ben Zakour, Alicia Fajardo-Lubian, Ariana Lopez Ayala, Jilong Qin, Makrina Totsika, Gaby van Galen, Jacqueline Norris, Jonathan Iredell.
Microbiology Spectrum, May 2022, Volume 10, Issue 3, https://doi.org/10.1128/spectrum.02158-21

The study, published under a Creative Commons License, can be read here

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