Extremely High Mortality Rates in Patients with Carbapenem-resistant, Hypermucoviscous Klebsiella pneumoniae Blood Stream Infections.

Background: Infections caused by carbapenem resistant K. pneumoniae are increasing and associated with high mortality rates. There are increasing reports of hypermucoviscous/ hypervirulent K. pneumoniae isolated from various sources. However, there is limited data on the prevalence of hypermucoviscous strains among carbapenem-resistant K. pneumoniae from invasive infections in India and its association with mortality. rmpA, rmpA2 and magA genes are associated with these hypervirulent strains. In this study, we investigate the prevalence of hypermucoviscous strains amongst carbapenem resistant K. pneumoniae isolated from blood culture. Association of mortality rate with meropenem minimum inhibitory concentration and hypermucoviscous strains are determined.

Methods: 86 non-repetitive carbapenem resistant K. pneumoniae isolated from bacteremia underwent E-test for meropenem minimum inhibitory concentration (MIC) determination and PCR for detection of carbapenamase genes. String test, PCR for rmpA, rmpA2 and magA were performed for characterisation of hypervirulent strains. Results: 31.3% of the 86 isolates displayed hypermucoviscous phenotype as indicated by a positive string test. Among the two genotypic markers, 7% were positive for rmpA2 and all were negative for rmpA and magA. 74.1% and 67.9% mortality were seen among string test positives and isolates meropenem MIC of ≥16µg/ml respectively (p 0.036 and 0.008 respectively). Isolates with both string positivity and meropenem MIC of ≥16µg/ml had a very high mortality rate of 84.2%.

Conclusion: String test, aids prediction of disease severity, and is independently associated with increased mortality in invasive carbapenem resistant K.pneumoniae health care-acquired infections. High meropenem MIC is a significant risk factor for mortality. Combination of string positive carbapenem resistant hypermucoviscous K. pneumoniae resulted in mortality rate of 84.2%. It is important to monitor prevalence of carbapenem resistant hypermucoviscous/hypervirulent K. pneumoniae among invasive isolates especially in a setting with high resistance rates as combination of increased virulence and decreased susceptibility to antimicrobials results in worse outcomes.