KPC: It’s the Drug Resistance, Stupid

Probably. With the recent CDC report detailing the many thousands killed by antibiotic resistance, a recent Antimicrobial Agents and Chemotherapy paper addresses a relevant question: in the clinical setting, are most drug-resistant infections dangerous (or lethal) because they are good at causing disease or because they are difficult to treat? In other words, are these strains highly virulent or just able to survive treatment?

From the abstract:

The virulence of a KPC-producing Klebsiella pneumoniae sequence type 258 (ST258) strain representing those circulating in Greece was assessed in a mouse septicemia model. The strain was virtually avirulent (50% lethal dose, >108 and 5 × 107 CFU for immunocompetent and neutropenic animals, respectively). Also, it was highly susceptible to serum killing, rapidly phagocytosed in vitro, and classified as K41, which is not among the virulent capsular types. The findings indirectly support the notion that high ST258-associated mortality is largely due to inefficient antimicrobial treatment.

To translate this from Biology into English, a huge dose is required to kill a mouse. Moreover, roughly the same dose is needed whether a mouse with or without normal amounts of white blood cells is used. Basically, this strain, which belongs to the most common clone of KPC Klebsiella pneumoniae–the predominant carbapenem resistant enterobacterial (‘CRE’) clone (these strains are resistant to just about everything, and mortality can be quite high)-is pretty weak as pathogens go.

Obviously, this isn’t the final word; it’s one strain of one clone, albeit a very deadly one–and one for which treatment is essentially nonexistent (it’s worth noting that the common E. coli version of CRE probably is good at causing disease). But it’s interesting that the real problem isn’t that this strain is good at causing disease, but that we can’t treat it. This might also explain why CRE infections are typically found in seriously ill patients–they have weakened immune systems and can’t fight off what is essentially a mediocre pathogen.

Cited article: Tzouvelekis LS, Miriagou V, Kotsakis SD, Spyridopoulou K, Athanasiou E, Karagouni E, Tzelepi E, Daikos GL. 2013. KPC-Producing, Multidrug-Resistant Klebsiella pneumoniae Sequence Type 258 as a Typical Opportunistic Pathogen. Antimicrob Agents Chemother. 2013 Oct;57(10):5144-6. doi: 10.1128/AAC.01052-13.

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