Wednesday, December 16, 2020

EID Journal: COVID-19 and Fatal Sepsis Caused by Hypervirulent Klebsiella pneumoniae, Japan, 2020

Credit EID Journal


While COVID-19 is viewed as primarily a viral disease, as with influenza, it can have bacterial co-conspirators. Reported incidence rates have varied widely between countries (see Bacterial Pneumonia in COVID-19 Critically Ill Patients: A Case Series), but a secondary bacterial pneumonia can greatly complicate treatment and recovery from COVID. 

Which is why last September - in #NatlPrep: Giving Your Preparedness Plan A Shot In The Arm - I wrote about getting the Prevnar Pneumococcal Vaccine PCV13) when I turned 66, even though I'd previously received the more common Pneumococcal polysaccharide vaccine (PPSV23).

These pneumonia vaccines don't provide full protection against all pneumococcal pneumonias, but they can greatly reduce your odds of acquiring a secondary bacterial pneumonia. 

Yesterday the CDC's EID Journal published an account of an elderly COVID patient in Japan who was co-infected with a hypervirulent form of Klebsiella pneumoniae.  HvKp is highly invasive, fairly common in Asia, and increasingly has been reported to have acquired significant antibiotic resistance (see CIDRAP Hypervirulent, highly resistant Klebsiella identified in China).

Complicating matters, dexamethasone - a corticosteroid - is one of the few pharmaceuticals that has proven useful in treatomg severe COVID-19 patients, even though its use may increase the chances of developing a secondary bacterial infection. The NIH's Rationale for Use of Corticosteroids warns:

In severe pneumonia caused by influenza viruses, corticosteroid therapy appears to result in worse clinical outcomes, including secondary bacterial infection and death. 

All of which makes it important to recognize, and treat, at-risk patients early in the course of their illness while at the same time, not over prescribing antibiotics, which may lead to greater antibiotic resistance. 

I've only posted some excerpts from a much longer report.  Follow the link to read it in its entirety, and I'll have a bit more when you return.  

COVID-19 and Fatal Sepsis Caused by Hypervirulent Klebsiella pneumoniae, Japan, 2020

Author affiliations: Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan (T. Hosoda, S. Ishino, M. Kaneko); The University of Tokyo Hospital, Tokyo, Japan (S. Harada, K. Okamoto, M. Mizoguchi); Fujita Health University School of Medicine, Aichi, Japan (M. Suzuki, R. Ito) 

A patient in Japan with coronavirus disease and hypervirulent Klebsiella pneumoniae K2 sequence type 86 infection died of respiratory failure. Bacterial and fungal co-infections caused by region-endemic pathogens, including hypervirulent K. pneumoniae in eastern Asia, should be included in the differential diagnosis of coronavirus disease patients with acutely deteriorating condition.
For a minority of patients, bacterial and fungal co-infections can complicate the course of coronavirus disease (COVID-19) (1,2). Co-infection can contribute to the poor prognosis for patients with COVID-19, especially for high-risk populations such as elderly patients (3).
Indeed, a large retrospective multicenter study reported that for half of the patients who died of COVID-19, secondary bacterial co-infection developed during hospitalization (3). In a retrospective study in China, the second most common respiratory pathogen detected from patients with COVID-19 was Klebsiella pneumoniae, following only Streptococcus pneumoniae (4).

Hypervirulent K. pneumoniae (hvKp) was originally recognized as a pathogen that causes severe community-acquired infections among relatively healthy persons. hvKp isolates carry virulence plasmids that harbor cardinal virulence genes, and with higher frequency than classical K. pneumoniae they cause disseminated infections involving liver, lungs, central nervous system, and eyes (5,6). 

Although hvKp infections have been reported mainly from hvKp-endemic areas such as eastern Asia, in recent years, sporadic cases have been increasingly reported worldwide (7). Furthermore, recent studies from hvKp-endemic areas demonstrated that hvKp is often associated with healthcare and hospitalization for elderly and debilitated populations (8,9). A multicenter study in Japan showed that more than half of bloodstream infections caused by hvKp occurred as healthcare-associated or hospital-acquired infections (8).

Therefore, hvKp infections may have the potential for seriously complicating the course of COVID-19, especially in hvKp-endemic areas. We describe a fatal case of superimposed hvKp infection in an elderly woman with COVID-19 in Japan.



For this COVID-19 patient who died of superimposed K. pneumoniae infection, the causative strain recovered from blood and sputum belonged to K2-ST86, a prototypical hvKp, together with K1-ST23. Furthermore, the isolate carried the cardinal hvKp virulence genes rmpA, rmpA2, iroBCDN, iucABCD, and peg-344, which have been recognized as molecular markers for the identification of hvKp that carry high risk for disseminated and fatal infections (6,8).

This case highlights 2 implications for the management of COVID-19 patients. First, bacterial and fungal co-infection may occur relatively early in the course of COVID-19. The condition of the patient reported here rapidly deteriorated 10 days after symptom onset; she had initially recovered after admission and treatment with dexamethasone. Although the timing (10 days after symptom onset) was typical for acute respiratory distress syndrome and acute cardiac injury resulting from COVID-19 itself (12), this patient instead experienced a fatal bacterial infection. 

Given the low prevalence of bacterial co-infections among COVID-19 patients, judicious use of antimicrobial drugs is recommended (13). However, this case emphasizes that timely antimicrobial treatment is crucial for patients with suspected or confirmed bacterial co-infection. Furthermore, corticosteroid treatment for COVID-19 may increase the risk for and severity of bacterial co-infection. 

Therefore, consideration for empiric antimicrobial therapy and thorough evaluation for bacterial co-infection should be considered for COVID-19 patients with acutely deteriorating condition. Second, local epidemiology should be considered when presuming a causative pathogen for patients with bacterial and fungal co-infections (14). Prevalence of hvKp infection in eastern Asia is exceptionally high (8). It is possible that a substantial number of superimposed hvKp infections complicating COVID-19 may have been unrecognized because the microbiological criteria for diagnosing hvKp widely used at microbiology laboratories in healthcare facilities (identifying carriage of genes for capsular genotype and string test) may not have been routinely available. 

For the case we report, respiratory colonization of hypermucoviscous K. pneumoniae was noted on culture at admission. Because colonization by hvKp is an established risk factor for subsequent hvKp invasive disease (15), additional caution is required for superimposed hvKp infections when caring for COVID-19 patients known to be colonized with hvKp.

In conclusion, we report a fatal case of hvKp infection superimposed on a patient with COVID-19. When the condition of COVID-19 patients worsens, bacterial and fungal infections, including region-endemic infections (hvKP in eastern Asia), should be included as a differential diagnosis and require appropriate evaluation and treatment in a timely fashion.
Dr. Hosoda is a clinician who specializes in infectious disease at the Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan. His research interests include hospitalization-associated disability resulting from COVID-19, especially for elderly patients.

Although most bacterial infections are still treatable - AMR (antimicrobial resistance) isn't some obscure future threat - as it already impacts millions of lives each year around the globe. In 2019, the CDC estimated that: More than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.  

While at-risk COVID patients must be treated (appropriately) with antibiotics, there are growing concerns that the heavy use of these antimicrobials during this pandemic could speed up the rise of antibiotic resistant organisms. 
Preventing the COVID-19 pandemic from causing an antibiotic resistance catastrophe - WHO

COVID-19 pneumonia and the appropriate use of antibiotics - The Lancet

Although I cover AMR topics from time to time in this blog, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about the growing global threat of AMR.

You'll also want to check out the CIDRAP-ASP Youtube Channel, which has more than 36 hours of lectures and webinars on Antimicrobial stewardship.

In this highly uncertain world, there are at least two things you can count on. 

  1. COVID-19 won't be the last pandemic to wreak havoc around the globe
  2. Evolutionary pressures due to overuse and misuse of antibiotics will continue to erode our limited armamentarium of these lifesaving drugs.
We either seriously prepare to deal with these looming biological threats, or we'll suffer the consequences.  Again.